Osteolytic bone disease is a frequent complication of multiple myeloma, resulting in skeletal complications that are a significant cause of morbidity and mortality. A characteristic feature of myeloma bone disease is that the lesions rarely heal and bone scans are often negative in myeloma patients who have extensive lytic lesions, offering very little in the follow-up of bone disease. X-rays are also of limited value in monitoring bone destruction during anti-myeloma or anti-resorptive treatment. Biochemical markers of bone turnover, such as N- and C-terminal cross-linking telopeptide of type I collagen (NTX, CTX/ICTP, respectively), and newer ones such as the tartrate resistant acid phosphatase isoform 5b, provide information on bone dynamics that in turn may reflect disease activity in bone. Several studies have shown bone markers to be elevated in myeloma patients and reflect the extent of bone disease, while in some of them bone resorption markers correlate with survival. These markers may also be helpful in identifying those patients likely to respond to bisphosphonate treatment, and monitoring the effectiveness of bisphosphonate therapy in the management of myeloma bone disease. This review attempts to summarize the existing data for the role of markers of bone remodeling in assessing the extent of bone destruction in myeloma and monitoring bone turnover during specific anti-myeloma treatment. We also discuss some novel markers that may be of particular interest in the near future.