Disorders of body composition, including obesity and osteoporosis, have reached record proportions. Coincidentally, our understanding of the mechanisms controlling body mass also has greatly improved. Shared regulation at the hypothalamus and the bone marrow highlight major bone–fat interactions. The hypothalamus modulates fat and bone via the sympathetic nervous system by regulating appetite, insulin sensitivity, energy use, and skeletal remodeling. In the bone marrow, fat and bone cells arise from the same stem cells. Insights from disorders such as anorexia nervosa provide a new rationale for examining the mechanisms that link bone to fat. This article explores these relationships in the context of a new paradigm with implications for obesity and osteoporosis.