This chapter focuses on the interaction of pathogens with the lower human respiratory tract (RT). The human RT can be divided into two regions: the nasopharynx, the most common site for bacterial colonization, and the lungs, which are sterile. The signature characteristic of bacteria that cause lower RT infection is the ability to adhere to and invade the mucosal epithelial cells (MECs)-either ciliated cells of the airways or type I and II alveolar cells in the terminal air sacs. To gain access to MECs, pathogens overcome the gauntlet of innate and specific defenses present in the mucosal secretions. These defenses routinely protect the host from the onslaught of commensal and pathogenic bacteria introduced into the RT daily. The most direct mechanism for protecting the host from bacteria is to kill the microbes prior to their contact with mucosal epithelial cells (MECs). A critical element making the mucous trap for bacteria effective-is the expulsion of secretions from the lower RT by the ciliary escalator. © 2005 Elsevier Inc. All rights reserved.