Transrectal ultrasound (TRUS) and prostate biopsy have become one of the most common office-based procedures for the practicing urologist. During the past 50 years, the techniques, indications, and pathologic interpretation of prostate biopsies have evolved. The abandonment of blind finger-guided needle biopsies in favor of systematic TRUS-guided biopsies epitomizes much of this change. Similarly, the indications for prostate biopsy have become more refined. In the past, the presence of a prostatic nodule on digital rectal examination (DRE) was the primary indication for biopsy until the introduction of prostatic-specific antigen (PSA) in the 1980s and its widespread use for prostate cancer screening. Abnormalities of PSA or its derivatives now represent the most common indication for prostate biopsy. Although TRUS initially began as a tool to direct needles into various locations within the prostate, today a great deal of information can be obtained from prostate ultrasound for the discerning clinician. As such, TRUS-guided biopsy of the prostate has become an important staging and diagnostic tool for the practicing urologist. Here we review the current techniques and indications as well as pertinent pathologic and staging data obtained through TRUS and prostate biopsy.