Articular cartilage is a complex, multilayered biological composite material, comprised of chondrocytes encapsulated in a water-based glycosaminoglycan matrix reinforced with collagen fibers. Once damaged by osteoarthritis or traumatic injury, this aneural, avascular tissue has little self-repair capacity. Over the last 20 years, cell therapies and tissue-engineering strategies have shown significant promise for the repair or regeneration of damaged cartilage. In particular, mesenchymal stem cells (MSCs) have great potential owing to their ability to create a reparative environment. Despite the fact that there have been great strides in the design and development of three-dimensional scaffolds, there is an upper limit to the number of viable cells that can be delivered using current approaches. To this end, this review examines current strategies for optimizing MSC localization, evaluates their limitations, and looks to other technologies to devise a combinatorial strategy for the creation of an MSC-seeded composite structure that addresses both the mechanical and biological property requirements for enhanced cartilage repair.