Up to 70% of prostate biopsies are negative in men with suspected prostate cancer. Because of inherent limitations in biopsy strategies, a significant proportion of cancers are missed on initial biopsy. Following negative biopsy, men frequently exhibit persistently elevated prostate-specific antigen - raising concerns for missed diagnosis. We highlight the recent updates in the management of negative prostate biopsy.Advances in noninvasive diagnostics are available and assist clinicians in further substratifying risk of prostate cancer. Despite limited data, urinary prostate cancer antigen 3 and transmembrane protease serine 2 appear to have a promising predictive value for patients suspected of prostate cancer. The advent of multiparametricMRI allows the visualization of intermediate and high-grade prostate cancer, particularly in the troublesome anterior prostate. This modality may further provide the potential for magnetic resonance-guided targeted biopsies. Current data suggest that in the presence of suspicious radiological findings, magnetic resonance-guided biopsies have superior sensitivity profiles compared with traditional rebiopsy approaches. In the absence of multiparametricMRI or suspicious findings, traditional saturation biopsies are sufficient.The management of negative biopsies is evolving rapidly with emerging diagnostics to stratify risk of prostate cancer in men with previous negative biopsies. An increasing body of information supports the use of magnetic resonance-guided biopsies.