Muscle spindles richly innervate muscles in vertebrates, providing critical sensory information about the body’s mechanical interactions with the environment necessary for neural control of movement. Muscle spindle afferent firing patterns have been well-characterized experimentally, but not fully explained mechanistically. I present a biophysical model demonstrates a range of well-known muscle spindle Ia afferent firing characteristics – including variations in firing due to prior movement history, and nonlinear scaling with muscle stretch velocity – emerge from first principles of muscle contractile mechanics. Simulating the mechanical interactions of intrafusal muscle fibers with muscle-tendon dynamics further reveal differential and interacting effects of motor commands to the muscle (alpha drive) and muscle spindle (gamma drive) on Ia firing, explaining highly variable activity during human voluntary force production and active muscle stretch. Our multiscale muscle spindle model provides a proof of concept of an extendable biophysical framework for understanding and predicting movement-related sensory signals in health and disease. I will provide specific examples of how a more sophisticated understanding of muscle and muscle spindle function can reveal mechanisms of motor disorders such as spasticity in cerebral palsy and rigidity in Parkinson’s disease, and how these mechanisms may be revealed through simple clinical tests founded on this physiological understanding.