Given the preclinical and clinical evidence supporting a specific role for the IGF system in cancer onset and progression, different approaches have been tested in the last 25 years to inhibit this axis, which resulted in the development of three major classes of targeted therapies: monoclonal antibodies (mAbs) targeting the IGF1R, TKIs, and neutralizing antibodies targeting IGF ligands. The gene discussed is IGF1; the disease is cancer.