Efforts to integrate music into healthcare systems and wellness practices are accelerating but the biological foundations that support this endeavor are not widely understood. As a result, music-based treatments remain on the fringe of medicine. In this review, I integrate progress in music research from neuroscience, psychology, and psychiatry to create a framework for translating between music’s specific foundations in human biology and its specific applications in mental health. This framework organizes the neurophysiological effects and clinical applications of music around four core elements of human musicality: tonality, rhythm, reward, and social connection. For each element, I review essential concepts, biological foundations, and evidence of clinical benefits. Working within this framework, I chart a path towards increasing the impact of music on health by quantifying individual differences in sensitivity to core elements of musicality and using them as a basis for increasing the precision with which musical treatments are applied. As such, I argue that biological insight into the origins, functions, and neural bases of music has an essential role to play in advancing the use music to improve human health and wellness.