The pleura responds to the presence of infecting organisms with a vigorous inflammatory response associated with an exudation of white blood cells and proteins. Changes in pleural permeability lead to formation of an exudative pleural effusion. The pleural mesothelial cell is the primary cell lining the pleural space and, when activated by the presence of organisms, initiates the inflammatory response by releasing a battery of chemokines and cytokines. Mesothelial cells are actively phagocytic and also release oxidants and proteases. The acute inflammatory process may resolve with appropriate antibiotic therapy and drainage leaving minimal fibrosis. However, under certain circumstances vigorous pleural fibrosis with scarring and loss of delineation of pleural surfaces can occur. Recognition of the stage of development of the empyema is an important clinical judgement that can affect outcome. The pathogenesis of infections of the pleural space and the role played by the various cell types is delineated in this article.