In recent years, the influence of the IGF system and insulin on cancer growth has been widely studied. Observational human studies have reported increased cancer mortality in those with obesity and type 2 diabetes, which may be attributable to hyperinsulinemia, elevated IGF-I, or potentially both factors. Conversely, those with low insulin, IGF-I and IGF-II levels appear to be relatively protected from cancer development. Initial attention focused on the role of IGF-I in tumor development. The results of these investigations allowed for the development of therapies targeting the IGF-I receptor signaling pathway. However, after in vitro and in vivo studies demonstrating that insulin may also play a significant and independent role in tumorigenesis, insulin is now receiving more attention in this regard. Some studies suggest that targeting insulin receptor signaling may be an important alternative or adjunct to targeting IGF-I receptor signaling. In this minireview, we discuss some of the recent in vitro, animal, and clinical studies that have elaborated our understanding of the influence of IGF and insulin on tumorigenesis. These studies have shed more light on the interaction between insulin and IGF signaling in cancer cells. They have made possible the development of novel targeted therapies and highlighted some of the potential future directions for research and therapeutics.