It is well known that infectious and inflammatory diseases such as sepsis and severe inflammatory response syndrome are accompanied by metabolic alterations such as insulin resistance. Conversely, metabolic diseases such as visceral obesity and type 2 diabetes are characterized by high levels of proinflammatory cytokines. Metabolism and immunity are linked by proteins of dual function. Adiponectin, a member of the C1q/TNF-related protein (CTRP) family, has attracted much interest because of its anti-inflammatory and insulin-sensitizing effects. To date, 15 additional CTRP family members have been identified that might also play a role in metabolism and immunity. This review focuses on the biochemistry and pleiotropic physiological functions of CTRPs as new molecular mediators connecting inflammatory and metabolic diseases.