Depending on the virus, humoral antibody may be an important component of host defense for neutralization of virions in their extracellular state. For highly cell associated virus like the Herpesviruses, cytotoxic mononuclear cells, with or without antibody dependence appear to be prime determinants influencing clinical recovery. Effective defense mechanisms depend on collaboration of different types of mononuclear cells, the release of soluble mediators like the interleukins and interferon, and are influenced by histocompatibility between effector and target cells. The advent of antiviral chemotherapy has not been nearly as dramatic as the development of agents which are effective against bacteria. Vaccines are effective for prevention of some diseases like influenza, measles and hepatitis. Killed immunogens rather than attenuated live virus vaccines are preferred for compromised hosts. Serum antibodies seem beneficial in preventing onset of H. zoster. Experimental cytomegalovirus (CMV) antibody preparations may prevent seroconversion in patients not receiving white cell transfusions. Two useful systemic agents for H. simplex and varicella-zoster infections are acyclovir and vidarabine but their effect against CMV is disappointing. Clinical studies with interferons are encouraging but all preparations have some toxicity and efficacy against CMV has not been demonstrated.