Trepanning of the bone is one of the oldest known procedures carried out by man and the use of the modern trephine biopsy has a venerable history. Parapia has published an admirable summary of the history of the topic and this should be consulted for the excellent illustrations of historical instruments [1]. The history is briefly summarized here [1]. Trepanning of the skull is the oldest known surgical procedure in humans and evidence of this practice has been found in Europe, North Africa, South America, Asia and New Zealand. In Peru, where the procedure is likely to have been carried out to treat headache, mental illness and to relieve intracranial pressure, sharp knives of obsidian, stone and bronze were used for trephination. Celsus, the Roman physician, described a modiolus – an iron instrument with a serrated cylinder that was rotated over a central pin by means of a strap. The early interventions were therapeutic and the first diagnostic biopsy was undertaken in Pianese in Italy in 1903. In 1922, Morris and Falconer used a drill-like instrument to biopsy the tibia, producing similar specimens to modern biopsies and, in the same year, Seyfarth developed a puncture needle for open biopsy of the sternum, producing smears, touch preparations and blocks for sectioning. The modern era probably began in 1958 when McFarland and Dameshek described a technique for biopsy of the right posterior iliac crest using a Silverman needle, which had been described in 1938. Further improvements followed, with modified instruments described by Jamshidi in 1971 and an electric drill technique by Burkhardt in 1971. Recent developments are described later in the chapter.