Obesity occurs when an excessive dietary fat intake leads to expansion of adipose tissue, which mainly consists of adipocytes that arise from proliferating and differentiating adipose stem cells, the preadipocytes. Obesity is a consequence of both adipocyte hypertrophy and hyperplasia. Knowledge about preadipocyte differentiation is relatively well established, whereas the mechanism responsible for preadipocyte proliferation is incompletely understood and only in the early stage of comprehension. In this regard, we have recently identified that Delta-like 1 homolog (Dlk1) (also known as Preadipocyte factor 1 [Pref-1]) inhibits preadipocyte proliferation by regulating their entry into G1/S-phase. This novel disclosure, adding to the previous published data on Dlk1 repression of preadipocyte differentiation, has given us the chance to firmly place Dlk1 as a master regulator of preadipocyte homeostasis and adipose tissue expansion. Dlk1 manipulation may, therefore, open new perspectives in obesity treatments.