The identification of an appropriate clinical question is critical for any biomarker project. Despite rapid advances in technology, few biomarkers have been forthcoming for prostate cancer. This could be because the clinical questions under investigation have not actually originated from clinical practice. These clinical questions are difficult to identify in the complex and heterogeneous pathogenesis of prostate cancer. In this Review, we have developed a prostate cancer 'roadmap' to identify the aspects of prostate cancer that may be amenable to biomarker discovery and serve as a guide for future projects in prostate cancer biomarker research.