Most commonly clinical or subclinical viral infections are self-limited by the effective immune response of the host leading to recovery. Occasionally, the infectious process may continue uncontrolled contributing to the demise of the patient or resulting in a number of sequelae, if the patient survives. This unfavorable outcome in a number of viral infections (e.g., those associated with herpes virus) usually reflects immunoincompetence (e.g., in transplant, cancer and AIDS patients). Conversely, dysregulation of immune functions (e.g., in autoimmunity) may triggered during the aftermath of certain viral infections. Recently, accumulated knowledge about the molecular biology of viruses has opened the way to more rational approaches to the development of more potent and more selective antiviral agents. In fact, some of these compounds have already been licensed for clinical use. Nonetheless, some of these antivirals which effectively affect viral replication may also possess significant immunosuppressive activity. Only in a few instances have antiviral agents been investigated for this interaction with the immune system and no attempts have been made to assess their potential immunosuppressive effects in the wide variety of assay systems for measuring the level of immunoreactivity. A correlation between the minimal antiviral concentration of the chemotherapeutic agent required to inhibit virus replication in cell culture and its minimal immunosuppressive concentration measured by lymphocyte responsiveness to mitogens or specific viral antigens has revealed different levels of efficacy (i.e., highest antiviral effect and lowest immunosuppressive activity): highest level as in the case of acyclovir (ACV) and bromovinyldeoxiuridine (BVDU) for HSV-1; moderate level as in the case of trifluridine (TFT). There are other chemotherapeutic agents whose efficacy is presently being evaluated regarding their interaction with the immune system. Other aspects of the management of the patient with viral disease include the clinical evaluation of biologic antivirals (e.g., interferon) and immunoenhancing substances designed to act through immunopotentiation of normal host responses. These studies should take into account: 1) the effect of these antiviral agents on each immune parameter of the host, particularly that which plays a major role in the resistance against the virus concerned; and, 2) the ratio of minimal antiviral concentration to the minimal immunosuppressive concentration to identify those agents or dosages that may impair the host’s immune response and, therefore, delay rather than speed the recovery process.