The goal of Epidemic is for the players, in their randomly selected roles, to work cooperatively to stop the spread of four diseases and cure them before a pandemic occurs.
The game consists of a game board representing a network connecting 48 cities on a world map, two decks of cards (Player cards and Infection cards), four colors of cubes with 24 cubes each (each representing a different disease), six Research Stations, and a pawn for each role. The Player cards include cards with each city name (the same as those on the board); Event cards, which can be played at any time (except for some events in expansions) to give the players an advantage; and Epidemic cards. Infection cards consist of one card for each city on the board and a color of the disease that will start there.
At the start of the game, Infection cards are randomly drawn to populate the board with infections, from one to three cubes for a number of cities. Players start at Atlanta, the home of the Centers for Disease Control, and are given a random role and a number of Player cards based on the number of players.
On each player's turn, there are four actions to take up, consisting of any combination of the eight possible actions (some of which require cards, including curing). After taking their actions, the player draws two Player cards, reducing their hand down to seven cards if necessary. If either draw is an Epidemic card, the player moves the Infection rate marker one space, draws a card from the bottom of the Infection deck and places three cubes on that city, puts that card into the Infection discard pile, reshuffles the discard pile, and places it back on top of the Infection deck (so that cards just drawn will come out again soon, unless another Epidemic follows shortly after). After the two Player cards are drawn (Epidemic or otherwise), a number of Infection cards are revealed (increasing throughout the game and corresponding to the Infection rate marker), and one cube of the indicated color is placed on each city drawn. Should a city already have three cubes and a new cube is to be added, an Outbreak occurs, and each interconnected city gains one cube of that color. This can create a chain reaction across many cities if several already have three disease cubes on them. After the infections are resolved, the player on the left has a turn.