Focal chondral defects of the articular surface are a common occurrence in the field of orthopaedics. These isolated cartilage injuries, if not repaired surgically with restoration of articular congruency, may have a high rate of progression to posttraumatic osteoarthritis, resulting in significant morbidity and loss of function in the young, active patient. Both isolated and global joint disease are a difficult entity to treat in the clinical setting given the high amount of stress on weightbearing joints and the limited healing potential of native articular cartilage. Recently, clinical interest has focused on the use of biologically active compounds and surgical techniques to regenerate native cartilage to the articular surface, with the goal of restoring normal joint health and overall function. This article presents a review of the current biologic therapies, as discussed at the 2015 American Orthopaedic Society for Sports Medicine (AOSSM) Biologics Think Tank, that are used in the treatment of focal cartilage deficiencies. For each of these emerging therapies, the theories for application, the present clinical evidence, and specific areas for future research are explored, with focus on the barriers currently faced by clinicians in advancing the success of these therapies in the clinical setting.