Exploration of outer space is a unifying endeavor for all of humanity. Indeed, two dozen countries have signed the Artemis Accords, signaling their commitment to shared values for long-term human exploration and research at the Moon and beyond. Yet, keeping humans healthy and productive during space travel remains a challenge. The musculoskeletal system is particularly sensitive to decrements in mechanical loading, such that bone and muscle loss are key concerns for long duration spaceflight. This presentation will review the impact of spaceflight on musculoskeletal health, and discuss possible interventions, including exposure to artificial gravity, to mitigate these effects.