There are standard guidelines for first transrectal ultrasonography (TRUS) guided biopsy in a patient presenting with elevated prostate-specific antigen (PSA) or suspicious digital rectal examination (DRE) findings. Patients are generally warned before a TRUS biopsy in respect of a false negative result. The clinical difficulty really arises in the presence of a persistently elevated PSA following an initial negative biopsy. Repeat prostate biopsies detect cancer in 16-41% of cases in which the initial biopsy was negative. In this article the authors succinctly describe the various options open to patients and clinician alike. With a low probability of finding a high-risk cancer on repeat biopsy (and with all the attendant biopsy-related complications) alternative options have to be considered. Abnormal pathology (prostatic intraepithelial neoplasia or PIN), atypical small acinar proliferation (ASAP) on previous biopsy, abnormal DRE, and transition zone volume were not significant predictors of a positive histology in repeat biopsies. Percent free PSA, PSA velocity, PSA density, and prostate cancer antigen three (PCA3) can all suggest a continued risk of malignancy in patients with a previous negative biopsy. A mean PSA velocity of 0.73ng/mL/year was associated with low-grade cancer on repeat biopsy, whereas a PSA volume of 5.73ng/mL/year was associated with intermediate-grade or high-grade cancer after an initial negative biopsy. The urine-based PCA3 is available and the Food & Drug Administration (FDA) has approved its use in risk stratification and for selecting patients for repeat biopsy - with a cut-off value of 25 or higher. Repeat biopsy should be directed to areas not previously sampled, such as the anterior portion, extreme apex and base, and midline. Changing the route of biopsy to a transperineal approach may improve the detection of anteriorly located cancers. Multi-parametric magnetic resonance imaging (MRI) shows the cancer location with higher sensitivity than TRUS and should be considered before repeat biopsy. The future role of MRI was discussed in detail in this year’s National Institute of Health & Care Excellence (NICE) guidelines on prostate cancer. Newer tumour markers, field defect markers and MRI / TRUS fusion technology may improve sensitivity and specificity of detection of prostate cancer.