In spite of the growing understanding of the fundamental biology of energy homeostasis, it is evident that crucial pathways have yet to be identified. Caveolins, integral plasma membrane proteins present in caveolae with proven scaffolding, transport and signalling capabilities, have emerged as key players in shifting the focus of obesity and insulin resistance development to lipid dynamics and membrane microdomain disorders. Caveolin-1-knockout mice exhibit a lean phenotype with overt resistance to diet-induced obesity. Conversely, caveolin-3-knockout mice show marked insulin resistance together with increased body weight and adiposity despite normal food intake. Here, we discuss the participation of caveolins as novel modulators of adipocyte biology, highlight their role in insulin signalling and outline their potential relevance to human obesity development and treatment.