The survival of the host depends upon an elaborate network of defenses that keeps harmful microbes and other foreign materials from penetrating the body. Should they penetrate, additional host defenses are summoned to prevent them from becoming established in tissues. Defenses involve barriers, cells, and chemicals, and they range from nonspecific to specific and from inborn to acquired. This chapter introduces the main lines of defense intrinsic to all humans. Topics included in this survey are the anatomical and physiological systems that detect, recognize, and destroy foreign substances and the general adaptive responses that account for an individual's long-term immunity or resistance to infection and disease.