For the last year or maybe year and a half, I have been playing a lot of Heads-up LHE, also known as HUHU. While I still have a ton to learn and am only Queen of the micros HUHU, so to speak, I can tell you, it's soo profitable, the swings and heartaches you have at 6max and even FullRing are making me play more and more Heads-up or extremely shorthanded games. I don't have any "wow" insights, so I'll just list a few general things to keep in mind when trying to play HUHU. Nothing revolutionary, just some advice. It is always a very slippery slope trying to teach/talking strategy about HUHU, since the fish pool is getting smaller and smaller these days (just look at the lobbies of the major online sites at the HUHU tables and you'll know what I mean).
Variance and stuff
Yes, standard deviation is way way way higher heads-up than any other form of poker, you'll have stretches where you don't win 10 hands in a row or maybe one in 20 and it'll be bad. You'll be like, where did my money go, I thought I was up 50BB? But if you're good, and most HUHU regs are amazingly good, then you'll have graphs that will make your jaw drop, you'll win and win and win and you'll be thinking, god it has to stop, right?
I was telling Doug the other day that while it is much easier to lose 100BB in HUHU, it is next to impossible to lose 300BB if you're a proven winner, don't tilt and play the right opponents, of course. 300BB downswings in 6max, while rare, are not unheard of. It is all just because of the winrate.
So, it sounds horrible to say, but the high winrate is what evens the swongs out. Look at some graphs of regular HUHU players (not mine, I actually sometimes play 6max). They really look like a constant upward graph, hardly any swings at all (even though there are some 100-150BB blips on there). Winrate is everything.
That is also the reason so many people moved to NL back in the day (4-5 years ago). Yes, the variance is higher, but booooy, the winrate is higher. I don't know if that still applies today's games, but it definitely applies to all forms of Heads-Up poker.
Bumhunting is the nuts
Never ever be proud. Ego will be your biggest downfall. I know, I've been there, I though: "I can take this guy, I have a small edge against him!" NO, NO, NO! Don't find out who's got the bigger balls, don't! Do as I say, not as I do on this one!
Saying: "no thx" even turns them on maybe. "oooh, she thinks I'm good, I can take on anybody!". If you find your opponent is half good, just sit him out after an even number of hands (so that each player gets to play an equal number of buttons). Don't try to "run well" or "I'm due".
Don't sit down with a breakeven player (for the most part), open a new table and wait, why would you want to give away rake? Sit down and wait! That is the downside of HUHU, you'll wait! Open other poker clients, open new 6max tables, open new FR tables, wait! Fish and tilted people want a game now! You have to look at this professionally, the fish will come.
Help! I have no bankroll
2/4 is about the limit where you want to start playing. Be even more selective there than at higher limits (although few good players go as far down as 2/4). Constantly check the lobby on who's sitting on other tables at 5/T and 3/6, so that you make sure that no shark sits with you. Uumm, try to find out if that player that just sat down is a winner or not, you know how!
But bellatrix, I only have bankroll for 1/2 or lower? Fine, HULHE SnG are a fine way to build up your bankroll, watch videos, try to apply some of that stuff to the SnG, that 2-10$ you lose in the SnG is not gonna kill your BR and you'll gain tons and tons of play.
Play uHULA, the team leaders will most likely have some sort of idea about HU play and will practice with you or at least go over your HHs or give you some advice.
Start new tables and leave as soon as there are 4 people on the table. Actually this one applies all the way to the highest limits

. But rake at 6max and FR tables only starts being collected at certain points, so often if you take down the pot on the flop it will often be rakeless. Learn the differences in the rake at different sites, they are important!
Stats, HUDs, numbers
Don't get hung up on numbers. Heads-up matches are extremely dynamic. My 3b! percentage preflop varies wildly from 0 to 40 for example (yes there are guys I never 3b). There are opponents you will play extremely aggressive against and some opponents you'll play more passive.
Having said that, if you run less than 70/40 (VPIP/PFR) preflop you are doing something wrong (should be more like 85/60). Stove it, try to find what 85% of hands is so that you know what to open on the button, you'll be amazed. The only thing is that stuff like 34 plays easier than 92, but you know what I mean.
Nits are the fish in HUHU poker. The loose, somewhat aggro guy who always SD in the FR games that you label a fish is actually extremely hard to play against. He may be clicking random buttons, but if he's showing down his hands down enough it's fine.
I hardly ever use a HUD playing HUHU. It's fine for showing which cards he SD with, but you can do that with "show last hand" feature. Sometimes knowing the 3b! percentage and WTSD is nice, but most opponents will adjust and or change based on you. Relying on the HUD might be even a hinderance as you won't grasp the nuances when the opponents is changing gears.
Momentum is a huge thing in HU play. It goes both ways, if opponent is hitting a lot of flops, he'll go ahead and raise his gutters and be very comfortable with his King high. Opponents on the losing side often get weak-tight tilt, because "you always have it". Take advantage of it! Pound pound pound until he gets it back!
Stop folding on the flop!
Gutshots are draws heads-up, 9-outers+ can be played for value or not, low boards are by default 6-outers or better. There are few flops that should be folded.
When you're out of position, your opponent will have a hard time to play against you, he'll have to value check tons of turns, so you often get free cards, he'll have to barrel his bluffs, so you often can showdown your A- or K-high profitably.
When you're in position, you can react easily. Try to make him think that he has no fold equity is basically the goal
Don't turn your Showdownable hands into bluffs
If you tell me you wanna value bet your A-high on the river, by all means, do it! There are some opponent like that, but usually these kinds of hands have super good SD value and the pot will lay you odds to call or c/c on the river.
The same goes with bluffing. If you are gonna bluff on a K72r flop to it with 83 and not A-high (unless you are doing it for value because somehow you can see your opponents' hole cards). A high has SD value.
Here comes a personal note. I see opponets going all crazy withs stuff like 4th or 5th pair. It's an ok hand, it's not a raising and not even 3b! hand on the river. SD SD SD! Having said that these are the kinds of hands where you will get your thin value from often...
State of mind
It's a game of waiting! If this is your job, when the 5th hitnrunner gets you for 20$ you will start to get frustrated. When the 5th river hits your opponent you might just become unraveled. Tilt gets magnified HU, you take stuff so personally. Relax! Look at your lifetime graph. Think af all those runner runnners you hit...
Be careful to observe the same thing in your opponents. Timing tells are huge in this. I swear I can sometimes *see* my opponents smashing their bet buttons because they are angry. Chat is wonderful of course. Cancer, accidents, slow deaths will be wished upon you. The sarcasm will just flow. If you are a girl you'll laugh at the different variations they find to spell the word c*nt. That's the time to get him, but don't spew. Note if they become nervous or start timing out when they are up a few bucks. They might be wanting to secure their winnings so you should semibluff more.
Last, but not least, one for Leroy: Don't openlimp your buttons