Protective immunity to chronic and acute viral infection relies on both the innate and adaptive immune response. Although neutralizing antibody production by B cells and cytotoxic activity of CD8(+) T cells are well-accepted components of the adaptive immune response to viruses, identification of the specific role of CD4(+) T cells in protection has been more challenging to establish. Delineating the contribution of CD4(+) T cells has been complicated by their functional heterogeneity, breadth in antigen specificity, transient appearance in circulation, and sequestration in tissue sites of infection. In this minireview, we discuss recent progress in identifying the multiple roles of CD4(+) T cells in orchestrating and mediating the immune responses against viral pathogens. We highlight several recent reports, including one published in this issue, that have employed comprehensive and sophisticated approaches to provide new evidence for CD4(+) T cells as direct effectors in antiviral immunity.