OX40, also known as tumor necrosis factor receptor superfamily (TNFRSF) 4 or CD134, is a co-stimulatory receptor, and it interacts with its ligand to provide positive signal for T cell activation. Disruption of the OX40 pathway led to defective T cell responses and overexpression of OX40 caused massive immune activation. Due to its importance in keeping immune homeostasis, strategies modulating the OX40 pathway hold great promise in fighting against cancer and autoimmune diseases.