In addition to storing and mobilizing energy, adipocytes secrete circulating factors to signal to other tissues and coordinate energy metabolism. These functions can become disrupted in the setting of obesity, contributing to the development of diabetes, cardiovascular disease, and cancer. Since the discovery of leptin and adiponectin, an increasing number of adipokines have been identified and their functions elucidated. More recent studies have highlighted other modes by which adipose tissue can participate in crosstalk with other cell types and tissues. These modes of communication, which are reviewed here, include the secretion of enzymes, lipid species, and exosomes. Advances in profiling technology suggest that a substantial number of adipose-derived factors remain to be characterized. Further advances in this growing field are likely to provide important basic insights into the molecular control of metabolism.