Trace elements as essential micronutrients play an important role in various physiological processes and are crucial for proper functioning of the immune system. Deficiency of trace elements and infectious diseases are often concomitantly observed and result in complex interactions. The major trace elements such as selenium, zinc, copper, manganese, etc. have immunomodulatory effects and thus influence susceptibility to and the course and outcome of a variety of viral infections. Some trace elements inhibit viral replication in the host cells and therefore have antiviral activity. Many trace elements act as antioxidants or are able not only to regulate the host immune response but also to alter the viral genome. This article gives a brief review of the major interactions between the trace elements and the immune system.