Damage to musculoskeletal tissues is a significant cause of morbidity and increased mortality, and is a magnifier of mortality in other clinical diseases such as diabetes and cardiovascular disorders. Innate repair capacities are limited for articular cartilage, tendon, and extensive bone defects, and current treatments for the repair of injured musculoskeletal tissue are not sufficient to restore the functionality of the original tissue. These daunting challenges necessitate a better understanding of musculoskeletal biology and emphasize the importance ofdiscovering novel repair and regeneration strategies that can be translated to clinical use. To discuss recent advances in translational research on musculoskeletal repair and regeneration, the Albert Einstein College of Medicine convened the Fourth Annual Musculoskeletal Repair and Regeneration Symposium in October 2015 in New York City. This Annals issue presents a collection of papers stemming from this symposium and discussing several current topics in musculoskeletal repair and regeneration, including the mechanisms and development of novel therapeutics for musculoskeletal diseases and the use of stem cells in tissue repair and regeneration.