Mucosal surfaces lining the lung and the gut are constantly exposed to environmental antigens, commensal organisms, and pathogens. Consequently, the host’s immune system devotes enormous resources to the defense of these tissues. Although mucosal immune responses must be sufficiently strong to eliminate pathogens, they must also have mechanisms to prevent excessive inflammation and initiate epithelial repair. Importantly, mucosal immune responses are initiated and regulated by a variety of mucosal lymphoid tissues, collectively known as mucosa-associated lymphoid tissue (MALT). This chapter describes the unique developmental, architectural, and functional features of the MALT and how those features facilitate the local immune response at each site.