Infectious pneumonias affect millions of individuals annually worldwide, accounting for unacceptably high mortalities in many populations. Following pathogen introduction to the lower respiratory tract by inhalation or aspiration, complex interactions between the host and the microbe determine whether the microbe is cleared or establishes an infectious pneumonia. Even modest variations in the host immune response to pathogens may have potentially profound impacts on pathogenesis, severity, and eventual survival of infectious pneumonias. In this article, the authors summarize the most common conditions that alter host defenses in a manner that predisposes to development of pneumonia.