Aijaz Parray,1 Hifzur R Siddique,1 Sanjeev Nanda,1,2 Badrinath R Konety,3 Mohammad Saleem1,3,41Molecular Chemoprevention and Therapeutics, The Hormel Institute, University of Minnesota, Austin, 2Department of Internal Medicine, Mayo Clinic Health Systems, Austin, TX, 3Department of Urology, University of Minnesota, Minneapolis, 4Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USAAbstract: The treatment landscape for patients with castration-resistant prostate cancer (CRPC) is undergoing significant changes with the advent of new therapies and multidisciplinary efforts by scientists and clinicians. As activation of multiple molecular pathways in the neoplastic prostate makes it impossible for single-target drugs to be completely effective in treating CRPC, this has led to combination therapy strategy, where several molecules involved in tumor growth and disease progression are targeted by a therapeutic regimen. In the present review, we provide an update on the molecular pathways that play an important role in the pathogenesis of CRPC and discuss the current wave of new treatments to combat this lethal disease.Keywords: chemoresistance, CRPC, molecular pathways, neoplastic prostat