It is currently believed that the development of a clinically relevant tumor needs new vessel formation provided by both angiogenesis (primary involving endothelial cells) and postnatal vasculogenesis (primary involving bone marrowderived cells). Clearly, it is important to identify factors that help to enhance the growth and “health” of tumors, as well as their further vascularization. The Insulin and Insulin-like Growth Factors (IGFs) systems play a key role in cellular metabolism, differentiation, proliferation, transformation and apoptosis, during normal and malignant growth. Moreover, these molecules seem essential in promoting tumor vascularization. Due to the complexity of these systems, the review has been focused on the role of insulin and IGFs signaling in the regulation of tumor angiogenesis and postnatal vasculogenesis. Since targeting on IGF for cancer therapy is rapidly becoming a clinical reality, a better understanding of IGFsmediated pathways has a relevant impact, providing new insights to help the design of newly developed drugs.