The insulin-like growth factor (IGF) system is a complex network of two soluble ligands; several cell surface transmembrane receptors and six soluble high-affinity binding-proteins. The IGF system is essential for normal embryonic and postnatal growth, and plays an important role in the function of a healthy immune system, lymphopoiesis, myogenesis and bone growth among other physiological functions. Deregulation of the IGF system leads to stimulation of cancer cell growth and survival. In order to manipulate the IGF system in the treatment of certain disorders, we must understand the protein-protein interactions at a molecular level. The complex molecular interactions of the ligands and receptors of the IGF system underlie all the biological actions mentioned above and will be the focus of this review.