Focal defects in articular cartilage are prevalent in the knee joint, with estimates indicating a prevalence of around 60%. Over recent decades, a variety of treatment approaches have been developed to address these focal cartilage defects. Smaller lesions may be treated with techniques such as debridement, marrow stimulation via microfracture, abrasion, drilling, and nano-fracture, in addition to advanced scaffold-augmented marrow stimulation methods, including AMIC, BST-Cargel, and GelrinC, as well as osteochondral autograft transplantation (OATS) or mosaicplasty. For larger defects, options such as osteochondral allograft (OCA) transplantation and autologous chondrocyte implantation (ACI) have proven to be effective. There is increasing interest in orthobiologic therapies involving mesenchymal stem cells (MSCs) and growth factors, with or without scaffolding, as a means to repair or regenerate articular cartilage. Orthobiologic scaffolds are designed with biological and chemical properties that cater to the requirements of tissue engineering applications, promoting the differentiation of cells into chondrocytes and facilitating the formation of hyaline cartilage. Numerous orthobiologic techniques enhanced by biologic scaffolds, such as the LIPO-AMIC procedure—which harmonizes autologous matrix-induced chondrogenesis with the concurrent application of autologous adipose-derived stem cells—have demonstrated safety and efficacy in treating chondral defects. As advancements in cartilage repair and regeneration continue, emerging treatment modalities will likely define the usefulness and effectiveness of orthobiologics while introducing novel strategies to enhance patient outcomes.