The synovial membrane undergoes a variety of structural changes throughout the pathogenesis of osteoarthritis (OA), including the development of fibrosis. Fibroblast-like synoviocytes (FLS) are a heterogenous cell population of the synovium that are suggested to drive the fibrotic response, but the exact mechanisms associated with their activation in OA remain unclear. Once activated, FLS are suggested to acquire a myofibroblast-like phenotype that drives fibrogenesis through excessive extracellular matrix (ECM) component deposition and an enhanced contractile function. In this review, we define FLS in the synovium, discuss how select extracellular or endogenous factors potentially induce their activation in OA, and describe how the activity of myofibroblast-like cells affects the structure of the synovial membrane.