The insulin-like growth factor signaling pathway is important in many human cancers based on data from experimental models as well as epidemiological studies. Important therapies targeted at this pathway have been or are being developed, including monoclonal antibodies to the insulin-like growth factor-I receptor and small molecule inhibitors of the tyrosine kinase function of this receptor. These investigational therapies are now being studied in clinical trials. Emerging data from phase I trials are encouraging regarding the safety of the monoclonal antibodies. In this manuscript, the rationale for targeting the insulin-like growth factor system is reviewed in addition to a summary of the available clinical trial data.