The ?/? hydrolase superfamily is comprised of diverse members that are involved in important biochemical processes and related to various diseases. They have unrelated sequences, various substrates, and different kinds of catalytic activities, yet they share the same canonical ?/? hydrolase fold, which consists of an eight-stranded parallel ?/? structure. They are also characterized by a catalytic triad composed of a histidine, an acid and a nucleophile. Members of this superfamily are often drug targets for treating diseases, such as diabetes, Alzheimer’s disease, obesity and blood clotting disorders. ABHD1 plays a role in metabolizing smoking xenobiotics. ABHD2 participates in the development of atherosclerosis. ABHD4 is involved in an alternative synthesis pathway of NAE. ABHD4 is a lysophospholipase selective for N-acyl phosphatidylethanolamine (NAPE) which participates in the biosynthesis of N-acyl ethanolamines. Mutations in ABHD5 contribute to Chanarin-Dorfman syndrome. ABDH6 may play a role in nervous system metabolism and signaling. ABHD14A is possibly involved in granule neuron development.