There is a growing interest in orthopedics and sports medicine in regenerative medicine, which incorporates tissue-engineering strategies: cells, scaffolds, and signaling molecules. Furthermore, patients seek “stem cells” or regenerative medicine treatments in response to unmet treatment needs and marketing efforts often outpacing clinical evidence and regulatory control. The application of biological therapies can facilitate the healing mechanism of tissues with limited healing potential and vascularity, such as tendons, cartilage, meniscus, and ligaments. However, to understand and advance the field of biological treatments, it is essential to understand the potential and limitations of the different components of tissue engineering approaches. Biological approaches commonly include platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and adipose tissue. Despite studies showing promising clinical results for cartilage injuries and ligament tears, conclusive clinical evidence is still missing. As such, there is a continued need for high-quality basic science and clinical investigation into the safety and efficacy of regenerative medicine, including cell-based therapies.