Only had this happen once so far, and thankfully it was in softcore. I was in a dungeon and my abilities stopped working. The ability icons for keys 1-4 + mouse icons and Evade would animate being depressed, but they wouldn’t do anything. I could still move my character around, though. I had to leave the game and re-enter to fix it.
I also saw that Skill Up on YouTube experienced this issue too as noted in their review (I recommend: Diablo IV (Spoiler-Free, Review-in-Progress) - YouTube).
FWIW:
- I had just unlocked my ultimate ability and assigned it to my bars; unsure if this is related, but might be a contributing factor.
- I am playing a Sorc
- I was in a dungeon (and so when I left/rejoined I had to redo it). I’m not 100% but IIRC it was the one to unlock Enchantments for my sorc.
You aren’t the only one to have experienced this bug. I just got done searching this forum for this bug (because it just happened to me) and found multiple complaints about it. Going back to the character select screen seems to fix it, but that is small comfort when you were almost done clearing a large dungeon.
experienced the same issue, but I was unable to reload back in to my character until after a good 15 minutes. It was stuck on loading screen to the dungeon, until it switched loading screen to open world for it to work
I got it twice, only fix I found is quitting game and restarting. Skills press visually but do not go off. Killed me twice too.
Same thing here… in Scosglen on surface so not too bad, a guildie got it at the end of a Stronghold and had to log out and redo the whole thing.
Can’t think of anything new I’d just done, got an Altar of Lilith maybe 30 seconds before. Skills and gear the same as they’d been the last 10 minutes.
Chiming in confirm both my wife and I experienced this issue.
I experienced it after leaving Kor Valar after completing the campaign quest there for the first time. Skills were working fine before I entered town, when I left none were responding. My wife’s skill were working fine at that time.
After leaving and re-entering the game (which did fix the issue), I teleported back to my wife’s character and we both entered the Zenith dungeon close by. As soon as we entered, my wife’s buttons stopped responding in precisely the same manner (but had been working fine against monsters outside the dungeon.) Leaving and re-entering the game fixed the problem for her as well.
All abilites stopped working after entering ‘Lights Watch’ for Side Quest ‘Legacies of Light’s Watch’
Q,1,2,3,4, Lclick, Rclick’ would not trigger attacks, but could still move.
Left and still no response. Pressing T teleported me. Did some blacksmith stuff, stash stuff, took portal back, still no response but could move. T no longer worked either by KB or pressing button on screen with mouse.
Ill chime in to add that this has also happened to me a few times. One time I was able to leave the dungeon and come back in and it reset it. But this last time I was doing the dungeon dealing with lilith and that womans mom. (lack of functioning brains cells prevents me from remembering names at the moment lol) Ive noticed that it happens to me when i portal to town and back, not any other time. And of course I cant portal back to see if it will reset. So now im going to be trying this all over agian. 
happend to me twice so far. Most recently in the middle of the capstone dungeon…
Just got this bug, almost by the end of the game =( sad hardcore player is sad.
Had this happen both in town and out in the field… in town I talked to an NPC what seemed like “too quickly” while it was still doing its quest dialog, and everything just greyed out, had to re-log. In another instance, in a dungeon, I’m not even sure what triggered it, there weren’t any enemies around - probably was from interacting with a lore item.
This has happened to me almost a dozen times now.
Only once was it at a really bad time but this bug definitely needs fixed as it’s extremely frustrating.
This just happened to me, lost my hardcore character with it. Was fighting Neyrelle’s mother, and then in the last 30% of the fight, could not use potion, dash, or use any abilities. Could still walk around with WSAD. Extremely frustrating to lose a hardcore character to a bug like this.
I see this issue on my Rog at least 4 times a dungeon or when there are massive monsters.
Have had this happen twice (sorc, controller on pc, both times in dungeons).
First time I couldn’t find a solve, quit out of game, relaunched.
Second time I thought to bring up and then close the Emote wheel; solved the issue w/o having to exit the game (and had no issues for the rest of the session, which was many hours long).
Had this happen an unable to get abilities back. After an obelisk called something like “storms fury made manifest” which overwrote all my keys for the duration of the buff, cool, but then didn’t give them back. tried relogging, switching world tier, respeccing all points, accepting sidequest, nada. My last season character still has abilities, but not this one. Quite frustrating.