Prostate cancer is the most commonly diagnosed cancer in men and is the second leading cause of cancer-related deaths in men each year. Androgen deprivation therapy is and has been the gold standard of care for advanced or metastatic prostate cancer for decades. While this treatment strategy initially shows benefit, eventually tumors recur as castration-resistant prostate cancer for which there are limited treatment options with only modest survival benefit. Upregulation of the insulin-like growth factor receptor type I (IGF-IR) signaling axis has been shown to drive the survival of prostate cancer cells in many studies. As many IGF-IR blockades have been developed, few have been tested preclinically and even fewer have entered clinical trials for prostate cancer therapy. In this review, we will update the most recent preclinical and clinical studies of IGF-IR therapy for prostate cancer. We will also discuss the challenges for IGF-IR targeted therapies to achieve clinical benefit for prostate cancer.