Caffeine is a member of the methylxanthine family of drugs, and is the most widely consumed behaviourally active substance in the western world. This article is focused on the impact of caffeine on immune function. In this regard, a number of in vitro and in vivo studies have demonstrated that caffeine modulates both innate and adaptive immune responses. For instance studies indicate that caffeine and its major metabolite paraxanthine suppress neutrophil and monocyte chemotaxis, and also suppress production of the pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha from human blood. Caffeine has also been reported to suppress human lymphocyte function as indicated by reduced T-cell proliferation and impaired production of Th-1(interleukin [IL]-2 and interferon [IFN]-gamma), Th-2 (IL-4, IL-5) and Th-3 (IL-10) cytokines. Studies also indicate that caffeine suppresses antibody production. The evidence suggests that at least some of the immunomodulatory actions of caffeine are mediated via inhibition of cyclic adenosine monophosphate (cAMP)-phosphodiesterase (PDE), and consequential increase in intracellular cAMP concentrations. Overall, these studies indicate that caffeine, like other members of the methylxanthine family, is largely anti-inflammatory in nature, and based on the pharmacokinetics of caffeine, we suggest that many of its immunomodulatory effects occur at concentrations that are relevant to normal human consumption. Finally, the potential of caffeine-induced immunomodulation to significantly impact upon health and well-being are discussed. (c) 2006 Elsevier Inc. All rights reserved.