Giant cell tumor (GCT) of bone is generally a benign tumor composed of mononuclear stromal cells and characteristic multinucleated giant cells that exhibit osteoclastic activity. It usually develops in long bones but can occur in unusual locations. The typical appearance is a lytic lesion with a well-defined but nonsclerotic margin that is eccentric in location, extends near the articular surface, and occurs in patients with closed physes. However, GCT may have aggressive features, including cortical expansion or destruction with a soft-tissue component. Fluid-fluid levels, consistent with secondary formation of aneurysmal bone cysts, are seen in 14% of cases. GCT can mimic or be mimicked by other benign or malignant lesions at both radiologic evaluation and histologic analysis. Rarely, GCT is associated with histologically benign lung metastases or undergoes malignant degeneration. In the past, the mainstay of treatment was surgical, primarily consisting of curettage with cement placement, with recurrence rates of 15%-25%. Recurrence is suggested by development of progressive lucency at the cement-bone interface. Other complications include pathologic fracture and postoperative infection. Denosumab, a monoclonal antibody that targets the osteoclastic activity of GCT, has produced 90% tumor necrosis in early studies, results indicative of promise as a potential adjuvant therapy.