The humerus is the second most common long bone site of metastatic disease, and the proximal third and diaphysis are frequent sites. Purely lytic disease and cortical bone destruction increase the risk of fracture more than 50%. For most patients, external beam irradiation is effective as a means of pain control and halting bone destruction. Fractures of the head or surgical neck can be treated with standard endoprostheses, whereas extensive proximal bone destruction is treated with custom proximal humeral replacements. Impending and complete diaphyseal fractures can be treated effectively with either intramedullary nail fixation or plate fixation. Rigid fixation, which can be achieved with dual plate fixation, is optimal because patients can begin immediate unrestricted activities using the upper extremity. Methylmethacrylate is an effective adjuvant for filling defects and for augmenting the fixation of intramedullary nails and screws. Postoperative external beam irradiation is necessary to prevent progressive bone destruction and subsequent loss of fixation.