Bisphosphonates, effectively used for metastatic bone disease and hypercalcemia, may evidentially have antiangiogenic properties. However, mechanism(s) of antiangiogenic effects of bisphosphonates are not fully understood. Their most pronounced effect is on metabolism of calcium, which is a main point of intersection for many distinct molecular signaling pathways that promote and modulate angiogenesis. An elevation of Ca(2+) plays a role in the mitogenic and secretory effects of growth factors. Some preclinical clues imply that antiangiogenic effects of bisphosphonates are related to its well-known hypocalcemic activity. Consequently, it may not be right to routinely recommend vitamin D and calcium supplementation to correct hypocalcemia unless it is symptomatic.