In the context of breast cancer, the importance of the skeleton in the regulation of primary tumour development and as a site for subsequent metastasis is well characterized. Our understanding of the contributions made by the host bone and bone marrow cells increasingly demonstrates the extent of the interaction between tumour cells and normal host cells. As a result, the need to develop and utilize therapies that can impede the growth and/or function of tumour cells while sparing normal host bone and bone marrow cells is immense and expanding. The need for these new treatments is, however, superimposed on the orthopaedic management of patients' quality of life, where pain control and continued locomotion are paramount. Indeed, the majority of the anticancer therapies used to date often result in direct or indirect damage to bone. Thus, although the bone microenvironment regulates tumour cell growth in bone, cells within the bone marrow niche also mediate many of the orthopaedic consequences of tumour progression as well as resistance to the antitumour effects of existing therapies. In this Review, we highlight the effects of existing cancer treatments on bone and the bone marrow microenvironment as well as the mechanisms mediating these effects and the current utility of modern orthopaedic interventions.