Percutaneous spine biopsy has widely replaced open biopsy during the last 50 years. Closed biopsy is more cost effective, less invasive, and has fewer complications than open procedures. A literature search was conducted in PubMed for percutaneous spine biopsy. The contributing factors to the success of the biopsy were identified by reviewing the articles and their references. These factors included location and type of lesion, needle system and use of different modalities of imaging as well as the physician’s expertise. Potential complications include pneumothorax, hematoma, nerve root injury, transient paresis, transient spinal anesthesia, meningitis, radiculopathy, and paraplegia. Overviews of the pre and post biopsy workup along with comprehensive description of the determinants of the biopsy outcome are discussed.