Cigarette smoke is a major health risk factor which significantly increases the incidence of diseases including lung cancer and respiratory infections. This increased susceptibility may result from cigarette smoke-induced impairment of the immune system. While the acute effects of cigarette smoke on the immune system are less clear, chronic exposure to cigarette smoke or nicotine causes T cell unresponsiveness. This apparent T cell anergy may account for or contribute to the immunosuppressive and anti-inflammatory properties of cigarette smoke/nicotine. Nicotine-induced immunosuppression may result from its direct effects on lymphocytes, indirectly through its effects on the neuroendocrine system, or both.