Basically, there are a number of different characters, weapons and rooms (6 suspects, 6 weapons and 9 rooms in the original). The owner of the mansion has been murdered and a certain suspect did it with a certain weapon in a certain room. Usually, each of the suspects/weapons/rooms has its own card, and at the start of the game, one of each category is randomly chosen and put into a folder - which contains the answers to who, where and how. The rest of the cards are randomly given out to all the players.
Now all the players must find out which three cards are in that folder. The cards that they hold in their own hand logically cannot have been involved in the murder, so they can rule them out. Then, players take turn to make suggestions as to who did it where and how. Each player has a figure on a board (which has the 9 rooms on it) and moves around by throwing 2 dice. When a player makes a suggestion, the next player has to show him one of the cards which has been suggested by the first player. (If he doesn't have any of those cards, the player after that one has to show one.) That is the main way of determining which cards the other players have. In the end, deduction should lead you to the answer - means you win if you know exactly which 3 cards are in the folder (because nobody else has them).