Articular cartilage is an avascular tissue that allows for frictionless mobility of joints. Unfortunately, cartilage is incapable of self-repair and any damage leads to degradation in osteoarthritis (OA). Autologous chondrocyte implantation therapies are currently being used to treat focal cartilage defects caused by post-traumatic OA (PTOA). For chondrocyte implantation, chondrocytes are isolated from healthy regions of cartilage from damaged joints, expanded on stiff polystyrene to increase cell number, and reimplanted into damaged areas to stimulate repair. Unfortunately, chondrocyte implantations can ultimately fail as chondrocytes dedifferentiate during expansion. In dedifferentiation, chondrocytes increase in size, elongate, and express contractile cytoskeletal molecules. Furthermore, cells produce a fibroblastic matrix which is biomechanically inferior to articular cartilage matrix. Therefore, developing a greater understanding of dedifferentiation is imperative. In the dedifferentiation process, cellular actin filaments reorganize from a cortical organization into stress fibers. The formation of stress fibers plays a crucial role in chondrocyte dedifferentiation by regulating chondrocyte cell morphology and gene expression. Determining the actin-based molecular underpinnings in chondrocyte dedifferentiation may enable the specific targeting of stress fibers to promote redifferentiation of passaged cells and improve chondrocyte implantation outcomes. This review focuses on how targeting regulators of actin filament organization may promote the redifferentiation of expanded chondrocytes for implantation, thus increasing potential therapeuticlongevity.