Summary: The T-helper 17 (Th17) lineage is a recently described subset of memory T cells that is characterized by its CD4+ status and its ability to make a constellation of cytokines including interleukin-17A (IL-17A), IL-17F, IL-22, and, in humans, IL-26. Although most extensively described in the autoimmunity literature, there is growing evidence that the Th17 lineage plays a significant role in mediating host mucosal immunity to a number of pulmonary pathogens. This review highlights our current understanding of the role of the Th17 lineage and Th17 cytokines in mediating mucosal immunity to both pulmonary and gastrointestinal pathogens. While we have the strongest evidence that the Th17 lineage is centrally involved in mediating the host response to Gram-negative extracellular pulmonary pathogens, this literature is rapidly evolving and demonstrates a central role for Th17 cytokines both in primary infection and in recall responses seen in vaccine studies. In this review, we summarize the current state of this literature and present possible applications of Th17-targeted immunotherapy in the treatment and prevention of infection.