Primary human preadipocytes in culture are characterized by a low proliferative capacity associated with a rapid decline of differentiation ability during subculturing; thereby limiting their use as cellular model. Cellular immortalization constitutes an interesting approach for establishing cell lines presenting an unlimited life span and a maintained differentiation capacity. Different procedures for developing immortalized human preadipocytes are discussed in this review. Transformation of human preadipocytes with the simian virus 40 large T-antigen (SV40 T-Ag) permitted the development of immortalized cells; however these cells could not maintain their capacity to differentiate into adipocytes. This limitation may be explained by the ability of SV40 T-Ag to inhibit transcriptional factors involved in the differentiation of preadipocyte. Reconstitution of the telomerase activity by stable expression of the hTERT (human telomerase catalytic subunit) gene was able to partially extend the lifespan of primary preadipocytes but not to promote cellular immortalization. However, a combined expression of hTERT and the E7 oncoprotein of human papillomavirus type 16, generated human preadipocytes with both an unlimited life span and a preserved adipogenic potential. This approach appears to be an effective method for establishing human preadipose cell lines for studying adipocyte differentiation and metabolism.