The short-chain fatty acid receptors FFA2 (GPR43) and FFA3 (GPR41) are activated by acetate, propionate, and butyrate. These ligands are produced by bacteria in the gut. In addition, the body itself can in particular produce acetate, and acetate plasma levels have been shown to be increased, e.g., in diabetic patients or during periods of starvation. FFA2 and FFA3 are both expressed by enteroendocrine cells and pancreatic β-cells. In addition, FFA2 is found on immune cells and adipocytes, whereas FFA3 is expressed by some peripheral neurons. It has therefore been speculated that short-chain fatty acid receptors are involved in the regulation of various body functions under different nutritional and metabolic conditions. Here we summarize recent data on the role of FFA2 and FFA3 in the regulation of metabolic, immunological, and neuronal functions and discuss the potential pharmacological relevance of this receptor system.