The natural history and clinical manifestations of tuberculosis in children differ significantly from those of the disease seen in adults. The two main factors determining the risk of progression to disease are patient age and immune status. Neonates have the highest risk of progression to disease, and in infancy miliary and meningeal involvement is common. Children from 5 to 10 years of age are less likely to develop disease than other age groups, and adolescent patients can present with progressive primary tuberculosis or cavitary disease. Immunocompromised patients are more likely both to progress to tuberculous disease and to have extrapulmonary manifestations; diagnostic tests are also of lower yield in this population. The most common sites of disease in children are intrathoracic disease and superficial lymphadenopathy. Clinical manifestations are often due to a profound inflammatory response to a relatively low burden of organisms. This is reflected in the low yield of diagnostic tests; consequently, the diagnosis of tuberculosis is often based upon a positive skin test, epidemiological information, and compatible clinical and radiographic presentation.