Sleep disturbance is one of the most prominent complaints of alcohol-dependent patients. In view of recent evidence that the immune system is integrated with other homeostatic processes ultimately regulated by the brain, the influence of sleep on host defense mechanisms and the expression of proinflammatory and T helper cell cytokines deserves attention in alcohol dependence. Although not all immune alterations found in alcohol-dependent persons are related to disordered sleep, it is exceedingly important to know whether sleep influences immunity in alcoholism because of the recognized impact of disordered sleep on infectious disease risk. Conversely, feedback systems are also operating between the brain and the immune system, and abnormalities in the expression of cytokines might contribute to sleep disturbances in alcohol-dependent persons. In this review, we identify the immune alterations found in association with alcohol dependence and discuss the implications of these findings for infectious disease risk, with particular attention to the interaction between African-American ethnicity and alcoholism in contributing to this risk. We provide evidence that sleep disruption occurs in association with alcohol dependence and that African-American alcohol-dependent persons show greater abnormalities in sleep and sleep regulatory processes than shown by Euro-American alcohol-dependent persons. The relations among alcoholism, sleep, and immunity are discussed, with an emphasis on understanding how the cytokine network is altered during sleep in the African-American alcohol-dependent populations. The potential is to use cytokine agonists or antagonists to determine whether physiologic changes in cytokines have a role in the homeostatic regulation of sleep in human beings, which has tremendous implications for the development of novel treatments of alcohol-related sleep disorders.