Prostate-specific antigen (PSA) is widely used as a biomarker in the detection of prostate cancer and for decision making regarding treatment options, response to therapy, and clinical follow-up. Despite its widespread use, it is well recognised that PSA has suboptimal performance as a screening tool due to poor specificity, resulting in high negative biopsy rates and potential 'over-diagnosis' and 'over-treatment' of clinically insignificant cancers. In particular, PSA does not reliably distinguish either cancer from benign prostatic conditions, or 'clinically significant' from 'indolent cancers', and it is inaccurate in predicting disease burden and response to treatment. There is an urgent demand for novel biomarkers to address these clinical needs. This article provides an update on the novel candidate biomarkers in development, which have shown potential for improving the detection of clinically significant cases of this malignancy.