The sympathetic nervous system regulates human immune system functions through epinephrine (Epi) and norepinephrine (NE) activation of adrenergic receptors (AR) expressed on immunocompetent cell populations. The anti-inflammatory effects that are most often attributed to increased sympathetic activity have been shown to occur through β2- and α2-AR stimulation. However, dichotomous AR effects on immune system function are becoming increasingly apparent. Reports of α1-AR expression on immune cell populations have been conflicting due to a lack of specific antibodies or subtype-selective receptor ligands. This has made α1-AR identification difficult and further characterization of α1-AR subtype expression limited. Nevertheless, there is some evidence suggesting an induction of α1-AR expression on immunocompetent cells under certain physiological conditions and disease states. Also, the function of α1-AR activation to modulate immune responses is just beginning to emerge in the literature. Changes in the secretion of inflammatory mediators as well as increased cell migration and differentiation have been described following α1-AR stimulation on immunocompetent cells. These observations demonstrate the significance of α1-AR activity in immune cell biology and emphasize the importance for understanding α1-AR effects on the immune system.