Leptin and adiponectin are hormones secreted from adipocytes that have important roles in metabolism and energy homeostasis. This review evaluates the effects of leptin and adiponectin on β-cell function by analyzing and compiling results from human clinical trials and epidemiologic studies as well as in vitro and in vivo experiments. Leptin has been shown to inhibit ectopic fat accumulation and thereby prevent β-cell dysfunction and protect the β-cell from cytokine- and fatty acid-induced apoptosis. However, leptin suppresses insulin gene expression and secretion as well as glucose transport into the β-cell. Adiponectin stimulates insulin secretion by enhancing exocytosis of insulin granules and upregulating the expression of the insulin gene; however, this effect depends on the prevailing glucose concentration and status of insulin resistance. In addition, adiponectin has antiapoptotic properties in β-cells. Available evidence concerning the role of these adipokines on insulin secretion, insulin gene expression, and apoptosis is not always entirely consistent; and many fundamental questions remain to be answered by future studies.