It is well accepted that aging is an important contributing factor to the development of osteoarthritis (OA). The mechanisms responsible appear to be multifactorial and may include an age-related pro-inflammatory state that has been termed “inflamm-aging.” Age-related inflammation can be both systemic and local. Systemic inflammation can be promoted by aging changes in adipose tissue that result in increased production of cytokines such as interleukin (IL)-6 and tumor necrosis factor-α (TNFα). Numerous studies have shown an age-related increase in blood levels of IL-6 that has been associated with decreased physical function and frailty. Importantly, higher levels of IL-6 have been associated with an increased risk of knee OA progression. However, knockout of IL-6 in male mice resulted in worse age-related OA rather than less OA. Joint tissue cells, including chondrocytes and meniscal cells, as well as the neighboring infrapatellar fat in the knee joint, can be a local source of inflammatory mediators that increase with age and contribute to OA. An increased production of pro-inflammatory mediators that include cytokines and chemokines, as well as matrix-degrading enzymes important in joint tissue destruction, can be the result of cell senescence and the development of the senescence-associated secretory phenotype (SASP). Further studies are needed to better understand the basis for inflamm-aging and its role in OA with the hope that this work will lead to new interventions targeting inflammation to reduce not only joint tissue destruction but also pain and disability in older adults with OA.