A comprehensive understanding of the molecular factors and regulatory mechanisms that contribute to osteoarthritis (OA) may establish innovative therapeutic strategies designed to influence the course of disease advancement. The prevailing conceptual framework surrounding OA is transitioning from a strictly mechanical ailment characterized by cartilage degradation to a multifaceted biological response interlinking biomechanics, inflammatory processes, and the immune system. Inflammatory mediators, encompassing cytokines including interleukin-1 and tumor necrosis factor α, pattern recognition receptors expressed on the surface such as toll-like receptors 2 and 4, complement components like C5, alongside pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), activate the enzymatic cascade responsible for cartilage matrix degradation in OA. By redefining the joint as a unified organ, the interactions among the resident cells within the synovium, comprising macrophages and a range of immune cell types, seem to promote enzymatic activity in cartilage, which subsequently transmits signals back to the synovium, reinforcing a feed-forward loop of degradation. This review proposes to analyze the prospective roles of immune cells, like macrophages and T cells situated in the synovium, in the facilitation and modulation of the inflammatory response characteristic of OA.