There are some proteins on the surfaces of lipid droplets (LDs) in the cells which could regulate the lipogenesis and lipolysis, and play an important role in lipid metabolism of the whole body. Comparative gene identification-58 (CGI-58), distributing predominantly on the surface of LDs, which is a member of the α/β-hydrolase folding family and an activator of adipose triglyceride lipase (ATGL) and acyl-CoA-dependent lysophosphatidic acid acyltransfer (LPAAT). CGI-58 promotes lipolysis by combining with perilipin which is a member of the PAT family and ATGL. At the same time, the function of CGI-58 to activate ATGL is influenced by protein-protein interaction with the members of the perilipin family. This paper reviews the CGI-58 function in lipid metabolism of animals considering the hot topics.