在Pandemic中，一些致命的疾病同时在世界各地爆发了！玩家们扮演的角色是抗病专家，任务是治疗疾病高发地区的人们并在四种瘟疫失控之前研究出对应的治疗方法。

游戏板描绘了世界上几个主要人口中心。在每一轮，每位玩家可以最多执行四个行动来穿梭于各个城市,治疗感染的人们，发现治疗方法或者建立一个研究站。一副牌为玩家提供了这些能力,但也夹杂着一些流行病卡牌，它能加快流行病的蔓延、加重病情。另一副独立的卡牌控制流行病以“正常”的速度传播感染。

在团队中扮演一个独特的角色,玩家必须计划与他们专家优势符合的战略网以征服疾病。例如，手术专家可以建造研究站，这是寻找治疗疾病方法所需要的，并且提高了城市间的移动性。科学家只需要一种特定疾病的4张卡牌就能治愈这种疾病，而其他专家需要5张。但是科学家选择的疾病会蔓延地更快。然而时间在本游戏中是有限的。如果一种或多种疾病的蔓延速度超过了治愈的速度或是时间流逝得太快，玩家们将集体失败。如果他们治疗了所有四种疾病,他们将全体获得胜利！

In Pandemic, several virulent diseases have broken out simultaneously all over the world! The players are disease-fighting specialists whose mission is to treat disease hotspots while researching cures for each of four plagues before they get out of hand.

The game board depicts several major population centers on Earth. On each turn, a player can use up to four actions to travel between cities, treat infected populaces, discover a cure, or build a research station. A deck of cards provides the players with these abilities, but sprinkled throughout this deck are Epidemic! cards that accelerate and intensify the diseases' activity. A second, separate deck of cards controls the "normal" spread of the infections.

Taking a unique role within the team, players must plan their strategy to mesh with their specialists' strengths in order to conquer the diseases. For example, the Operations Expert can build research stations which are needed to find cures for the diseases and which allow for greater mobility between cities; the Scientist needs only four cards of a particular disease to cure it instead of the normal five—but the diseases are spreading quickly and time is running out. If one or more diseases spreads beyond recovery or if too much time elapses, the players all lose. If they cure the four diseases, they all win!