Castration-resistant prostate cancer remains incurable and a major cause of mortality worldwide. The absence of effective therapeutic approaches for advanced prostate cancer has led to an intensive search for novel treatments. Emerging nanomedical approaches have shown promising results, in vitro and in vivo, in improving drug distribution and bioavailability, tumor penetration and in limiting toxicity. Nanoscaled carriers bearing finely controlled size and surface properties such as liposomes, dendrimers and nanoparticles have been developed for successful passive and active tumortargeting. Enhanced pharmacokinetics of nanotherapeutics, through improved target delivery and prolonged tissue halflife provides optimal drug delivery that is tumor-specific. Tumor-targeting may be improved through ligand directed delivery systems binding to tumor-specific surface receptors improving cellular uptake through receptor-mediated endocytosis. Recently published data have provided pre-clinical evidence showing the potential of active-targeted nanotherapeutics in prostate cancer therapy; unfortunately, only a few of these therapies have translated into early phase clinical trials development. Hence, progress of active-targeted nanotherapy improving efficiency of site-specific drug delivery is a critical challenge in future clinical treatment of prostate cancer. Exploring specific prostate cell-surface antigens or receptor overexpression may elaborate promising strategies for future therapeutic design. This review presents an overview of some new strategies for prostate cancer active-targeting nanotherapeutics.