The sympathetic nervous system integrates the functions of multiple organ systems by regulating their autonomic physiological activities. The immune system is regulated both locally and systemically by the neurotransmitters epinephrine and norepinephrine secreted by the adrenal gland and local sympathetic neurons. Immune cells respond by activation of adrenergic receptors, primarily the β2-adrenergic receptor, which signal through heterotrimeric G-proteins. Depending upon the cell type, adrenergic signaling regulates a variety of functions in immune cells ranging from cellular migration to cytokine secretion. Furthermore, due to the diurnal oscillation of systemic norepinephrine levels, various immune functions follow a circadian rhythmic pattern. This review will highlight recent advances in our understanding of how the sympathetic nervous system regulates both innate and adaptive immune functions and how this regulation is linked to circadian rhythms.