Complementary and alternative medicines (CAMs) are used in more than 80% of the world's population and are becoming an increasing component of the US health care system, with more than 70% of the population using CAM at least once and annual spending reaching as much as $34 billion. Since the inception of the National Center for Complementary and Alternative Medicine, there has been an enormous increase in the number of basic science and therapy-based clinical trials exploring CAM. The subspecialty of allergy and immunology represents a particularly fertile area with a large number of CAM therapies that have been shown to affect the immune system. Recent work has uncovered potential biochemical mechanisms involved in the immunomodulatory pathway of many supplemental vitamins (A, D, and E) that appear to affect the differentiation of CD4+ cell TH 1 and TH 2 subsets. Other research has shown that herbs such as resveratrol, quercetin, and magnolol may affect transcription factors such as nuclear factor-κB and the signal transducer and activator of transcription/Janus kinase pathways with resultant changes in cytokines and inflammatory mediators. Clinically, there have been hundreds of trials looking at the effect of CAM on asthma, allergic rhinitis, and atopic dermatitis. This article reviews the history of CAM and its use among patients, paying special attention to new research focusing on herbals, phytochemicals, and vitamins and their potential interaction with the immune system.