Innate host defense pathways consist of microbial sensors, their signaling pathways, and the antimicrobial effector mechanisms. Several classes of host defense pathways are currently known, each comprising several pattern-recognition receptors that detect different types of pathogens. These pathways interact with one another in a variety of ways that can be categorized into cooperation, complementation, and compensation. Understanding the principles of these interactions is important for better understanding of host defense mechanisms, as well as for correct interpretation of immunodeficient phenotypes.