The covalent attachment of palmitic acid to one or more cysteine residues (S-palmitoylation) is a widespread modification of signalling proteins. With the finding that palmitoylation is a dynamic process, it is now widely accepted that repeated cycles of palmitoylation/depalmitoylation could be involved in the regulation of multiple signalling processes. Palmitoylation also represents a common post-translational modification of the GPCRs (G-protein-coupled receptors). Functionally, palmitoylation of GPCRs has been shown to play a central role in the regulation of multiple receptor functions, including determining the efficiency and selectivity of G-protein coupling, receptor phosphorylation and desensitization, endocytosis and transport to the plasma membrane. The present review summarizes our current knowledge of the palmitoylation of serotonin (5-hydroxytryptamine) receptors and its role in the regulation of receptor functions.