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. These determinants are: lesion type; location of the lesion in the vertebrae and the level of the spine where the lesion is located; the imaging guidance used to identify the lesion during biopsy; and, the needle or trephine which is used to obtain the specimen. A detailed review of different approaches used to penetrate the lesion by trephine or needle are also provided. The decision on how the surgeon should obtain a percutaneous spine biopsy is dependent on the characteristics of the lesion, availability of imaging guidance and also the expertise of the physician.