One main motivation for the study of viruses is the fact that they cause many important infectious diseases, among them the common cold, influenza, rabies, measles, many forms of diarrhea, hepatitis, Dengue fever, yellow fever, polio, smallpox and AIDS. Herpes simplex causes cold sores and genital herpes and is under investigation as a possible factor in Alzheimer's.

Some viruses, known as oncoviruses, contribute to the development of certain forms of cancer. The best studied example is the association between Human papillomavirus and cervical cancer: almost all cases of cervical cancer are caused by certain strains of this sexually transmitted virus. Another example is the association of infection with hepatitis B and hepatitis C viruses and liver cancer.

Some subviral particles also cause disease: the transmissible spongiform encephalopathies, which include Kuru, Creutzfeldt–Jakob disease and bovine spongiform encephalopathy ("mad cow disease"), are caused by prions, hepatitis D is due to a satellite virus.

The study of the manner in which viruses cause disease is viral pathogenesis. The degree to which a virus causes disease is its virulence.

When the immune system of a vertebrate encounters a virus, it may produce specific antibodies which bind to the virus and neutralize its infectivity or mark it for destruction. Antibody presence in blood serum is often used to determine whether a person has been exposed to a given virus in the past, with tests such as ELISA. Vaccinations protect against viral diseases, in part, by eliciting the production of antibodies. Monoclonal antibodies, specific to the virus, are also used for detection, as in fluorescence microscopy.

A second defense of vertebrates against viruses, cell-mediated immunity, involves immune cells known as T cells: the body's cells constantly display short fragments of their proteins on the cell's surface, and if a T cell recognizes a suspicious viral fragment there, the host cell is destroyed and the virus-specific T-cells proliferate. This mechanism is jump-started by certain vaccinations.

RNA interference, an important cellular mechanism found in plants, animals and many other eukaryotes, most likely evolved as a defense against viruses. An elaborate machinery of interacting enzymes detects double-stranded RNA molecules (which occur as part of the life cycle of many viruses) and then proceeds to destroy all single-stranded versions of those detected RNA molecules.

Every lethal viral disease presents a paradox: killing its host is obviously of no benefit to the virus, so how and why did it evolve to do so? Today it is believed that most viruses are relatively benign in their natural hosts; some viral infection might even be beneficial to the host. The lethal viral diseases are believed to have resulted from an "accidental" jump of the virus from a species in which it is benign to a new one that is not accustomed to it (see zoonosis). For example, viruses that cause serious influenza in humans probably have pigs or birds as their natural host, and HIV is thought to derive from the benign non-human primate virus SIV.

While it has been possible to prevent (certain) viral diseases by vaccination for a long time, the development of antiviral drugs to treat viral diseases is a comparatively recent development. The first such drug was interferon, a substance that is naturally produced when an infection is detected and stimulates other parts of the immune system.