3 centre backs just get ripped apart with wingers pulling them out wide and if they leave the wingers to the wing backs it leaves 3 centre backs in the middle covering 1 or 2 strikers which is a waste of a player.
It gets more complicated when delivering the ball from the keeper as well.
You now dont have two full backs with chalk on their boots to pick up the ball meaning you have to deliver to a centre half instead (delivering to a full back is the better play as the team without the ball wont push wingers up so high whilst not in possession - most top sides full backs will move straight to the touchline when their keeper has the ball).
Now if an attacking midfielder pushes up covering the third man you have to kick every time, effectively here you are giving up a decent proportion of moves you can start on the ground from the back.
(Note Hiddink's excellent tactics in the CL quarter at Anfield last season where he had Malouda pick up Arbeloa as the third man and Liverpool had awful possession all night)
This is the one reaon I believe a 3-5-2 works better with world class wing backs such as Cafu and Roberto Carlos rather than out and out wingers.
But just because it presents new tactical challenges it doesn't mean with the right personnel it wont work.