Human adenoviruses are among a growing number of human, animal, and even plant viruses that encode gene products that interfere with the defense mechanisms of the host. The host mechanisms most often affected by these viral products are the innate and inflammatory responses such as interferon and the proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF). This review discusses examples of viral anti-immune mechanisms from many different viruses and then focuses on the molecular interactions between adenoviruses and TNF and the effect of these interactions on the ensuing pathogenesis of virus infection.