#1 Turn off all AV products (I have no idea why people have been saying that AV products interfere with trainers, my previous 3 AVs and my current one has never interfered with any trainers before 0.o)

#2 Check game version, check trainer version. Both must be the same for them to work. Usually trainers modify certain memory locations in game. After a new patch these locations might have been modified and cause the trainer to not be able to recognise them/modify them. A new trainer will most probably be released with every new patch for the newer and more popular games.

#3 If you are using Vista, run BOTH the GAME and the TRAINER as administrator. And i don't mean logging in with an administrator account to run them. I mean, right-click on both the trainer and game shortcuts/exes, and clicking "Run As Administrator".

Vista doesn't give a damn if you are using an administrator account. All programs that are run are still treated as running in a standard account unless told otherwise.