The metastasis of cancer cells to bone alters bone architecture and mineral homeostasis. As described by the ‘seed and soil’ hypothesis, bone represents a fertile ground for cancer cells to flourish. A ‘vicious cycle’ of reciprocal bone–cancer cellular signals occurs with osteolytic (bone-resorbing) metastases, and a similar mechanism likely modulates osteoblastic (bone-forming) metastatic lesions as well. The development of targeted therapies either to block initial cancer cell chemotaxis, invasion and adhesion or to break the ‘vicious cycle’ is dependent on a more complete understanding of bone metastases. Although bisphosphonates delay progression of skeletal metastases, it is clear that more-effective therapies are needed. Cancer-associated bone morbidity remains a major public health problem, and to improve therapy and prevention it is important to understand the pathophysiology of the effects of cancer on bone. This review details scientific advances in this area.