Pathogen persistence in the respiratory tract is an important preoccupation, and of particular relevance to infectious diseases such as tuberculosis. The equilibrium between elimination of pathogens and the magnitude of the host response is a sword of Damocles for susceptible patients. The alveolar macrophage is the first sentinel of the respiratory tree and constitutes the dominant immune cell in the steady state. This immune cell is a key player in the balance between defense against pathogens and tolerance toward innocuous stimuli. This review focuses on the role of alveolar macrophages in limiting lung tissue damage from potentially innocuous stimuli and from infections, processes that are relevant to appropriate tolerance of potential causes of lung disease. Notably, the different anti-inflammatory strategies employed by alveolar macrophages and lung tissue damage control are explored. These two properties, in addition to macrophage manipulation by pathogens, are discussed to explain how alveolar macrophages may drive pathogen persistence in the airways.