Components of the immune system at the tissue and cellular level receive circadian information by means of neural and endocrine signals. Most immune cells contain molecular clock components. These cellular clocks mediate immune responses in natural killer cell activity, macrophage cell phagocytosis, and inflammation. This chapter explores how the circadian regulation of the immune system contributes to the maintenance of an adequate and robust immune response. It focuses more specifically on various components of the immune system and on how they are affected by the interaction with the circadian system. The chapter shows that key immune cells are regulated by the circadian system. It describes on the effects of circadian disturbance on health and disease. Disturbance of clock function through genetic manipulation also elicits changes in the regulation of the immune system.