Prostate cancer (PCa) diagnostic and therapeutic work-up has evolved significantly in the last decade, with pre-biopsy multiparametric MRI now widely endorsed within international guidelines. There is potential to move away from the widespread use of systematic biopsy cores and towards an individualised risk-stratified approach. However, the evidence on the optimal biopsy approach remains heterogeneous, and the aim of this review is to highlight the most relevant features following a critical assessment of the literature. The commonest biopsy approaches are via the transperineal (TP) or transrectal (TR) routes. The former is considered more advantageous due to its negligible risk of post-procedural sepsis and reduced need for antimicrobial prophylaxis; the more recent development of local anaesthetic (LA) methods now makes this approach feasible in the clinic. Beyond this, several techniques are available, including cognitive registration, MRI-Ultrasound fusion imaging and direct MRI in-bore guided biopsy. Evidence shows that performing targeted biopsies reduces the number of cores required and can achieve acceptable rates of detection whilst helping to minimise complications and reducing pathologist workloads and costs to health-care facilities. Pre-biopsy MRI has revolutionised the diagnostic pathway for PCa, and optimising the biopsy process is now a focus. Combining MR imaging, TP biopsy and a more widespread use of LA in an outpatient setting seems a reasonable solution to balance health-care costs and benefits, however, local choices are likely to depend on the expertise and experience of clinicians and on the technology available.