Insulin-like growth factor (IGF)-mediated signaling pathways have long been recognized as important targets for cancer therapy. The development of antibodies against the IGF type I receptor (IGF-IR) started in the early 1980s, although clinical studies of these antibodies were not conducted until more recent years. At least eight different anti-IGF-IR antibodies are currently in clinical trials and are reviewed in this article; each antibody was generated by a different method and has unique features. Information collected from these early clinical trials should be taken into consideration during the design of further studies and future clinical applications, as well as in the improvement of the respective antibodies. The development of antibodies against IGF ligands is also discussed.