<p>Interorgan communication between bone and skeletal muscle is central to human health. A dysregulation of bone–muscle crosstalk is implicated in several age-related diseases. Ageing-associated changes in endocrine, inflammatory, nutritional and biomechanical stimuli can influence the differentiation capacity, function and survival of mesenchymal stem cells and bone-forming and muscle-forming cells. Consequently, the secretome phenotype of bone and muscle cells is altered, leading to impaired crosstalk and, ultimately, catabolism of both tissues. Adipose tissue acts as a third player in the bone–muscle interaction by secreting factors that affect bone and muscle cells. Physical exercise remains the key biological stimulus for bone–muscle crosstalk, either directly via the release of cytokines from bone, muscle or adipocytes, or indirectly through extracellular vesicles. Overall, bone–muscle crosstalk is considered an inherent process necessary to maintain the structure and function of both tissues across the life cycle. This Review summarizes the latest biomedical advances in bone–muscle crosstalk as it pertains to human ageing and disease. We also outline future research priorities to accommodate the understanding of this rapidly emerging field.</p>