PURPOSE Epidemiological studies have found an inverse association between acute infections and cancer development. In this paper, we review the evidence examining this potentially antagonistic relationship. METHODS In addition to a review of the historical literature, we examined the recent epidemiological evidence on the relationship between acute infections and subsequent cancer development in adult life. We also discuss the impact of chronic infections on tumor development and the influence of the immune system in this process. RESULTS Exposures to febrile infectious childhood diseases were associated with subsequently reduced risks for melanoma, ovary, and multiple cancers combined, significant in the latter two groups. Epidemiological studies on common acute infections in adults and subsequent cancer development found these infections to be associated with reduced risks for meningioma, glioma, melanoma and multiple cancers combined, significantly for the latter three groups. Overall, risk reduction increased with the frequency of infections, with febrile infections affording the greatest protection. In contrast to acute infections, chronic infections can be viewed as resulting from a failed immune response and an increasing number have been associated with an elevated cancer risk. CONCLUSION Infections may play a paradoxical role in cancer development with chronic infections often being tumorigenic and acute infections being antagonistic to cancer.