Osteolytic bone lesions from advanced multiple myeloma (MM) result in significant skeletal morbidity. Therefore, biochemical markers of bone metabolism, such as the N-terminal and C-terminal telopeptides of type I collagen, bone-specific alkaline phosphatase, and osteocalcin, have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity, and response to antiresorptive treatment. Several studies have shown that the majority of biochemical markers of bone metabolism are increased in patients with MM with osteolytic bone lesions, thus reflecting changes in bone metabolism associated with tumor growth. There is also a growing body of evidence that markers of bone metabolism correlate with the risk of skeletal complications, disease progression, and death. In addition, bone markers could potentially be used as a tool for early diagnosis of bone lesions. The aim of this review is to improve our understanding of bone markers as a clinical tool for the management of malignant bone disease in patients with MM.