Osteoarthritis (OA) is the most common form of arthritis, affecting nearly 140 billion dollars in annual healthcare expenditures in the United States alone. Risk factors for OA include obesity, aging, and joint injury, but the underlying mechanisms remain unclear. Recent evidence suggests that cellular dysregulation and inflammation in joint tissues, including intra-articular adipose tissue, may contribute to disease severity. The infrapatellar fat pad (IFP), located in the knee joint, serves as a protective cushion and secretes multiple endocrine factors and inflammatory cytokines, playing a role in joint physiology and disease. Inflammation and fibrosis of the IFP are correlated with cartilage degeneration and OA-associated disease severity. This article reviews recent progress in understanding the roles and regulation of intra-articular fat tissue in regulating joint biology and OA. Aging and obesity lead to increased IFP size and chronic inflammation, with larger IFP volumes positively correlated with clinical symptoms and pain. Obesity induces expansion and pathologic remodeling of the IFP, similar to other white adipose tissue (WAT) depots. Aging causes maladaptive accumulation of senescent cells that produce inflammatory cytokines and matrix-degrading enzymes, contributing to OA pathology. The IFP produces factors that can affect disease progression through paracrine mechanisms, including cytokines, adipokines, growth factors, and fatty acids. Adipokines such as leptin, resistin, and adiponectin are implicated in OA development and have complex immunomodulatory effects. The IFP is also a source of mesenchymal stem cells (MSCs) that can modulate inflammation and potentially play a role in joint tissue repair. Early modulation of inflammation in the IFP and synovial membrane may be a promising disease-modifying strategy, and the reparative and immunomodulatory functions of MSCs derived from the IFP offer potential therapeutic avenues for OA treatment.Osteoarthritis (OA) is the most common form of arthritis, affecting nearly 140 billion dollars in annual healthcare expenditures in the United States alone. Risk factors for OA include obesity, aging, and joint injury, but the underlying mechanisms remain unclear. Recent evidence suggests that cellular dysregulation and inflammation in joint tissues, including intra-articular adipose tissue, may contribute to disease severity. The infrapatellar fat pad (IFP), located in the knee joint, serves as a protective cushion and secretes multiple endocrine factors and inflammatory cytokines, playing a role in joint physiology and disease. Inflammation and fibrosis of the IFP are correlated with cartilage degeneration and OA-associated disease severity. This article reviews recent progress in understanding the roles and regulation of intra-articular fat tissue in regulating joint biology and OA. Aging and obesity lead to increased IFP size and chronic inflammation, with larger IFP volumes positively correlated with clinical symptoms and pain. Obesity induces expansion and pathologic remodeling of the IFP, similar to other white adipose tissue (WAT) depots. Aging causes maladaptive accumulation of senescent cells that produce inflammatory cytokines and matrix-degrading enzymes, contributing to OA pathology. The IFP produces factors that can affect disease progression through paracrine mechanisms, including cytokines, adipokines, growth factors, and fatty acids. Adipokines such as leptin, resistin, and adiponectin are implicated in OA development and have complex immunomodulatory effects. The IFP is also a source of mesenchymal stem cells (MSCs) that can modulate inflammation and potentially play a role in joint tissue repair. Early modulation of inflammation in the IFP and synovial membrane may be a promising disease-modifying strategy, and the reparative and immunomodulatory functions of MSCs derived from the IFP offer potential therapeutic avenues for OA treatment.