Clarification of the aetiology of chronic human diseases such as atherosclerosis or cancer is one of the dominant topics in contemporary medical research. It is believed that identification of the causal factors will enable more efficient prevention and diagnosis of these diseases and, in some instances, also permit more effective therapy. The task is difficult because of the multistep and multifactorial origin of these diseases. A special case in contemporary aetiological studies is definition of the role of viruses in the pathogenesis of human cancer. Virus–associated cancer develops only in a small minority of infected subjects, which implies that, if the virus does play a role in the pathogenesis of the malignancy, other factors must also be involved. In this paper the author attempts to review the present methodological approaches to aetiological studies of chronic diseases, discusses the role of criteria for identifying causal relationships and proposes guidelines that might help to determine the role of viruses in human cancer.