<p>Prostate cancer remains a major cause of cancer morbidity and mortality and is rising in incidence across the world. Although a succession of randomised controlled trials have improved outcomes across all stages of disease, there remain significant clinical challenges and unmet needs. Repurposed drugs have attracted interest in the treatment of prostate cancer, where a number of agents have been proposed with a range of mechanisms of action suggesting potential benefits. A major advantage of such drugs is the wealth of pre-existing patient safety data typically available, meaning repurposed agents would be expected to have a known and often low toxicity profile and also (as often late in their developmental pathway and hence generic drugs are available) attractive in terms of cost effectiveness. The evidence required for repurposed drugs to become accepted standards of care and enter the treatment formulary however is no less arduous than conventional development pathways, where confirmatory results from randomised phase III trials remain the absolute requirement. Additionally, these efforts are often led by academic trial groups – with challenges then in the steps to licensing that are typically undertaken by industry. To date, despite large scale initiatives, there is a paucity of drugs successfully repurposed in this way. Using examples across the different clinical scenarios we discuss the opportunities and challenges, design and analyses of current phase III trials testing repurposed drugs for the treatment of patients with prostate cancer and highlight where future success may come.</p>