Free fatty acid receptors (FFAs) are highly enriched in enteroendocrine cells providing pathways to link dietary fats and microbially generated short-chain fatty acids (SCFAs) to the secretion of a variety of gut hormones. FFA1 and FFA4 are receptors for long-chain fatty acids that have been linked to the elevation of plasma gut hormones after fat ingestion. FFA2 and FFA3 are receptors for SCFA, which are generated at high concentrations by microbial fermentation of dietary fiber and have also been implicated in enhancement of gut hormone secretion. FFAs are candidate drug targets for increasing the secretion of intestinal hormones such as glucagon-like peptide-1 and peptide YY as potential new treatments for type 2 diabetes and obesity. This review will examine aspects of intestinal physiology and pharmacology related to the function of FFAs in enteroendocrine cells.