The insulin-like growth factor (IGF) system performs multiple functions in normal tissue. IGFs are involved in normal mammary gland development, but have also been implicated in the pathogenesis of breast cancer. Epidemiological studies found an association between elevated serum levels of IGF-I and an increased risk for breast cancer. IGF-I is the major mediator of growth hormone (GH) action. On the cellular level, IGF-I has a strong influence on cell proliferation and it is a potent inhibitor of apoptosis. Further, IGFs are also involved in angiogenesis. These characteristics are the basis for their involvement in maintenance and progression of cancer. The functions of IGF-I are mainly mediated through the type-I IGF-receptor (IGF-IR). The availability of free IGF-I for interaction with IGF-IR is modulated by IGF binding proteins (IGFBP 1–6). Based on interactions with other receptors, including estrogen and epidermal growth factor receptors, combined targeted therapies may improve breast cancer treatment.