Patients with multiple myeloma often experience skeletal-related complications including pathological fractures, hypercalcemia, spinal cord compression, pain requiring surgery or radiotherapy. Myeloma bone disease is characterized by the presence of lytic lesions due to increased osteoclastic activity, which is not accompanied by a comparable increase in bone formation. Targeting osteoclastic bone resorption therefore represents an important approach to treating patients with myeloma-related bone disease. Bisphosphonates are potent inhibitors of osteoclast activity and function. Recent large, placebo-controlled clinical trials have shown the efficacy of bisphosphonates in reducing skeletal complications in multiple myeloma and suggest that these agents may also alter the overall course of the disease. In this review, we summarize the data covering the effect of different types of bisphosphonates on myeloma bone disease, their mode of action and the future implications of their use.