Epidemiological studies have reported an increased risk of cancer in people with type 2 diabetes (T2DM) and obesity, related in part to hyperinsulinemia, secondary to insulin resistance. Hyperinsulinemia leads to increased expression of insulin-like growth factor (IGF)-I expression. In fact, increased insulin, IGF-I and IGF-II levels are associated with tumor growth in vitro, in animal models, and in epidemiological studies in humans. In this paper, we discuss the roles of insulin, IGF-I and IGF-II, their interaction with the insulin receptor (IR) and IGF-I receptor (IGF-IR), and their signaling pathways and regulation as these pertain to tumor growth. We explain how these pathways have been deciphered by in vitro and in vivo studies, and how they are being exploited in the development of targeted cancer therapies.