Osteoarthritis (OA), the most common form of arthritis, is a major cause of pain and disability, affecting one in seven adults in the US. It is characterized by progressive cartilage damage, bone spurs, and synovial inflammation, often affecting the knee. Obesity, aging, and joint injury are major risk factors for OA, with aging and obesity contributing to chronic inflammation and the accumulation of senescent cells, which secrete inflammatory factors. The infrapatellar fat pad (IFP), a key adipose tissue in the knee, plays a critical role in joint health and OA progression. The IFP provides cushioning, secretes inflammatory cytokines (inflammaging), and interacts with other joint tissues to regulate joint function. Obesity and aging lead to IFP enlargement and chronic inflammation, which are associated with cartilage defects and OA severity. The IFP is a source of cytokines, adipokines, and growth factors that influence joint inflammation and fibrosis. Adipokines such as leptin, resistin, and adiponectin are involved in OA pathogenesis, with elevated levels linked to disease severity. IFP-associated macrophages and lymphocytes contribute to inflammation and fibrosis in OA. The IFP also plays a role in OA pain, with increased IFP signal intensity and fibrosis correlating with pain levels. IFP remodeling and fibrosis are associated with OA progression, and anti-fibrotic treatments may alleviate pain. The IFP is a potential source of mesenchymal stem cells (MSCs) for cartilage repair and immunomodulation. Understanding the role of the IFP in OA could lead to new therapeutic strategies, including targeting inflammation and fibrosis in the joint.Osteoarthritis (OA), the most common form of arthritis, is a major cause of pain and disability, affecting one in seven adults in the US. It is characterized by progressive cartilage damage, bone spurs, and synovial inflammation, often affecting the knee. Obesity, aging, and joint injury are major risk factors for OA, with aging and obesity contributing to chronic inflammation and the accumulation of senescent cells, which secrete inflammatory factors. The infrapatellar fat pad (IFP), a key adipose tissue in the knee, plays a critical role in joint health and OA progression. The IFP provides cushioning, secretes inflammatory cytokines (inflammaging), and interacts with other joint tissues to regulate joint function. Obesity and aging lead to IFP enlargement and chronic inflammation, which are associated with cartilage defects and OA severity. The IFP is a source of cytokines, adipokines, and growth factors that influence joint inflammation and fibrosis. Adipokines such as leptin, resistin, and adiponectin are involved in OA pathogenesis, with elevated levels linked to disease severity. IFP-associated macrophages and lymphocytes contribute to inflammation and fibrosis in OA. The IFP also plays a role in OA pain, with increased IFP signal intensity and fibrosis correlating with pain levels. IFP remodeling and fibrosis are associated with OA progression, and anti-fibrotic treatments may alleviate pain. The IFP is a potential source of mesenchymal stem cells (MSCs) for cartilage repair and immunomodulation. Understanding the role of the IFP in OA could lead to new therapeutic strategies, including targeting inflammation and fibrosis in the joint.