Orthobiologics therapies in the knee are a relatively new and rapidly evolving field that use biological treatments to help repair and regenerate damaged tissues in the knee. These therapies include stem cells, platelet-rich plasma (PRP) and other growth factors to promote healing and reduce inflammation. The use of orthobiologics has gained considerable interest in recent years for the treatment of a variety of musculoskeletal pathologies. As ‘natural’ treatments, they represent an attractive option for patients and surgeons that can be used in conjunction with traditional surgical procedures for augmentation, or in isolation as an alternative to surgery in a minimally-invasive manner. While orthobiologics therapies hold great promise in the treatment of knee conditions, there have been a variety of challenges to the widespread use of these therapies, including ambiguity in nomenclature, leading to confusion among consumers and providers, biologic heterogeneity, regulatory challenges and a lack of well-designed level one studies evaluating these agents that adequately report variables critical to outcome or assess purity/potency of treatments delivered. This article will provide an overview of the current orthobiologic options for the treatment of orthopaedic pathologies in the knee, as well as a discussion surrounding the current evidence and associated controversies.