The concepts of nonresolving and progressive pneumonia are difficult to define: both refer to a failure in the therapeutic response, which in the case of progressive pneumonia may cause a medical emergency even in the first 72 hours after empiric treatment. The incidence of nonresolving pneumonia in community-acquired pneumonia is approximately 10%, and greater than 30% in nosocomial pneumonia. Mortality in nonresponding pneumonia increases 3-fold in community-acquired and 5-fold in nosocomial pneumonia compared with global mortality in hospitalized patients. Factors associated with the resolution of pneumonia are related to the host, the microorganisms, and the cytokine response that modulates the relationship between them. Causes of nonresolving or progressive pneumonia may be infectious or noninfectious. Management of nonresponding patients requires a reevaluation of epidemiologic data, a complete microbiologic investigation, with conventional and invasive respiratory samples, and performance of a new radiographic study. Empiric therapeutic changes are aimed at broadening bacteriologic coverage to treat resistant or unusual microorganisms.