Certain types of cancers have a strong propensity to metastasize to bone, which requires combination of multiple factors responsible for the different steps of metastasis. Bone metabolic markers are now widely used in clinical practice and give useful information on the ongoing bone metabolism, reflecting the activity of bone-resorbing osteoclasts and bone-forming osteoblasts. Bone markers have a potential as diagnostic tools for bone metastasis, and are useful in monitoring the response to anticancer as well as antiresorptive therapies. Since bone metabolic markers alone are insufficient for the diagnosis and assessment of bone metastasis, it is important to combine bone markers with tumor-related markers and imaging studies such as scintigraphy and MRI. More recently, soluble receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) have been implicated as markers for osteoclastogenic activity. Serum levels of these factors and/or their ratios may provide additional information on the severity of bone disease and the prognosis.