Children account for a major proportion of the global tuberculosis disease burden, especially in endemic areas. However, the accurate diagnosis of childhood tuberculosis remains a major challenge. This review provides an overview of the most important recent advances in the diagnosis of intrathoracic childhood tuberculosis: (1) symptom-based approaches, including symptom-based screening of exposed children and symptom-based diagnosis of active disease; (2) novel immune-based approaches, including T cell assays and novel antigen-based tests; and (3) bacteriological and molecular methods that are more rapid and/or less expensive than conventional culture techniques for tuberculosis diagnosis and/or drug-resistance testing. Recent advances have improved our ability to diagnose latent infection and active tuberculosis in children, but establishing a diagnosis of either latent infection or active disease in HIV-infected children remains a major challenge, particularly in high-burden settings. Although improved access to diagnosis and treatment is essential, ultimately the burden of childhood tuberculosis is determined by the level of epidemic control achieved in a particular community. Several recent initiatives, in particular the United Nations Millennium Developmental Goals, deal with the problem of poverty and disease in a holistic fashion, but global political commitment is required to support these key initiatives.