Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in OA pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating certain protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with OA, and possible therapeutic approaches to target neutrophils for the treatment of OA are described. Since neutrophils play a complex role in the pathophysiology of osteoarthritis, contributing to joint degradation as well as joint repair, targeting these cells is likely to pave the way for a potential therapeutic approach for the management of OA. Future studies are needed to investigate the use of targeted therapies to modulate neutrophil function and identify their subpopulations that are associated with osteoarthritis progression or response to treatment.