Osteoarthritis (OA) is the most common degenerative disease affecting joint tissues. The pathogenesis of OA is complex and poorly understood, as well as the multiple factors contributing to its development and progression. Accumulating evidence has suggested that microRNAs (miRNAs) play an important role as regulators of cartilage biology and in the pathogenesis of OA. It has been demonstrated that mechanical loading, important for the regulation of cartilage metabolism, affects miRNAs expression. Furthermore, miRNAs present in human plasma and in synovial fluid could represent promising biological markers for OA. Herein, we have reviewed the current state of research on miRNAs in cartilage homeostasis and OA pathogenesis and their potential clinical applications.