This chapter provides an in-depth exploration of cartilage, a pivotal component crucial for joint health, particularly within the context of osteoarthritis (OA). It delves deeply into the intricate structure and dynamic functions of articular cartilage, elucidating its essential roles in load-bearing, shock absorption, and maintaining joint stability. Emphasizing the delicate balance of cellular components, such as chondrocytes, and extracellular matrix constituents like proteoglycans and collagens, which collectively ensure the mechanical and biological integrity of cartilage, the discussion places significant attention on factors influencing cartilage homeostasis and contributing to its eventual degradation, analyzing age-related changes, mechanical stress, and genetic predispositions, alongside the impact of inflammatory processes and cytokine imbalances. By highlighting the multifaceted interplay among these factors, a clear narrative emerges, elucidating the initiation of OA. Furthermore, the chapter investigates into the cascade of events that define OA pathogenesis, dissecting the underlying mechanisms responsible for cartilage damage and matrix degradation, tracing their combined contribution toward the development of OA. In its focus on OA’s etiology, the chapter underscores importance of comprehending cartilage alterations as a critical starting point for designing therapeutic interventions aimed at effectively managing OA.