The insulin-like growth factors (IGFs), their binding proteins (IGFBPs) and structurally related proteins have been identified in adipose tissue but their roles in adipose tissue are poorly understood. IGF-I and IGFBP-3 expression increase during human preadipocyte differentiation. However, whereas IGF-I stimulates this process, IGFBP-3 is inhibitory both to preadipocyte differentiation and to differentiated adipocyte function. The direct interaction of IGFBP-3 with peroxisome proliferator-activated receptor-gamma is believed to contribute to its inhibitory effect on differentiation. Connective tissue growth factor (CTGF/CCN2) shares weak structural homology and functional similarities with IGFBP-3, including inhibition of preadipocyte differentiation. This review examines the current knowledge of IGFBP regulation and actions in adipocytes and proposes a common regulatory pathway involving IGFBP-3 and CTGF/CCN2.