Research in various disciplines has highlighted that humans are uniquely able to solve the problem of cooperation through the informal mechanisms of reputation and gossip. Reputation coordinates the evaluative judgments of individuals about one another. Direct observation of actions and communication are the essential routes that are used to establish and update reputations. In large groups, where opportunities for direct observation are limited, gossip becomes an important channel to share individual perceptions and evaluations of others that can be used to condition cooperative action. Although reputation and gossip might consequently support large-scale human cooperation, four puzzles need to be resolved to understand the operation of reputation-based mechanisms. First, we need empirical evidence of the processes and content that form reputations and how this may vary cross-culturally. Second, we lack an understanding of how reputation is determined from the muddle of imperfect, biased inputs people receive. Third, coordination between individuals is only possible if reputation sharing and signaling is to a large extent reliable and valid. Communication, however, is not necessarily honest and reliable, so theoretical and empirical work is needed to understand how gossip and reputation can effectively promote cooperation despite the circulation of dishonest gossip. Fourth, reputation is not constructed in a social vacuum; hence we need a better understanding of the way in which the structure of interactions affects the efficiency of gossip for establishing reputations and fostering cooperation.