Following detection of high levels of serum prostate-specific antigen, many men are advised to have transrectal ultrasound-guided biopsy in an attempt to locate a cancer. This nontargeted approach lacks accuracy and carries a small risk of potentially life-threatening sepsis. Worse still, it can detect clinically insignificant cancer cells, which are unlikely to be the origin of advanced-stage disease. The detection of these indolent cancer cells has led to overdiagnosis, one of the major problems of contemporary medicine, whereby many men with clinically insignificant disease are advised to undergo unnecessary radical surgery or radiotherapy. Advances in imaging and biomarker discovery have led to a revolution in prostate cancer diagnosis, and nontargeted prostate biopsies should become obsolete. In this Perspective article, we describe the current diagnostic pathway for prostate cancer, which relies on nontargeted biopsies, and the problems linked to this pathway. We then discuss the utility of prebiopsy multiparametric MRI and novel tumour markers. Finally, we comment on how the incorporation of these advances into a new diagnostic pathway will affect the current risk-stratification system and explore future challenges.