This chapter discusses giant cell tumor of bone. Giant cell tumor (GCT) of bone was first described by Sir Astley Cooper in 1818. It is the most common benign bone tumor encountered by an orthopedic surgeon and has a well-known propensity for local recurrence after surgical treatment. Giant cell tumors are generally symptomatic in the majority of patients. The knee is the most common site followed by the distal radius. Role of chemotherapy and radiotherapy, Role of embolization and bisphosphonates, pathology, differential diagnosis, and treatment of giant cell tumor are also discussed in this chapter.