The field of orthobiologics has experienced a dramatic increase in the last years. Researchers and clinicians now realize that restoring anatomy, function, and improving symptoms has to involve biology. The most commonly investigated and applied orthobiologics are platelet-rich plasma (PRP) and stem cells. The present book chapter summarizes the existing evidence regarding clinical studies investigating the effectiveness of PRP and stem cells for a number of soft tissue injuries and disorders of the knee: ligament injuries, tendon injuries, meniscal injuries, focal cartilage injuries, and knee osteoarthritis.