The lung is constantly exposed to airborne infectious agents due to the large surface area of approximately 100 m2. Therefore, pneumonia is one of the most common lung diseases. Understanding infection requires understanding the routes of infections, the way invading organisms infect epithelial cells, as well as the defense mechanisms of the lung acquired during evolution. Several defense systems have been developed during the evolution of the respiratory system, from the old phagocytic system, to the mucociliary escalator system, and finally to the immune system, which all protect the lung. Besides alveolar pneumonias, more specific forms such as granulomatous pneumonia exist, which is based on a specific action of the immune system, to remove organisms which cannot be cleared by other leukocytes. Finally, fibrosing pneumonia has caused a lot of investigations, because of the dismal outcome of some variants. Molecular analysis of these different diseases is an emerging new tool for the differential diagnosis, for identification of the underlying etiology, and in some times also predicting prognosis.