Mass Effect 3. Yes, it's coming. When? Holiday 2011 - it seems like a long time from now, but I promise it'll go fast. ME3 was revealed at the 2010 Video Game Awards with a teaser without gameplay (like all the rest of the teases).
Before the awards show, EA briefly listed the game on it's site with the following spiel:
Earth is burning. Striking from beyond known space, a race of terrifying machines have begun their destruction of the human race. As Commander Shepard, an Alliance Marine, your only hope for saving mankind is to rally the civilizations of the galaxy and launch one final mission to take back the Earth.
There were large changes from the original Mass Effect to the sequel, but expect big changes for the third (and possibly last) Mass Effect game. It's also a good nod toward Sony PS3 owners with it being announced that it's coming out on all 3 platforms at once.