Although it comprises a substantial proportion of the tuberculosis (TB) burden, particularly in developing communities, childhood TB was until recently largely neglected. North American researchers and clinicians have made substantial contributions to our knowledge of TB in children; their findings, gathered mostly before the availability of chemotherapy, remain an irreplaceable source of learning for modern practice, decision making and TB control, and pose questions regarding TB pathophysiology that remain unanswered. By the time chemotherapy was introduced, it was known that very young children were extremely susceptible to serious disease and that adolescence was a period when there was a transition in the underlying natural response to infection to one characterised by necrotising lung lesions associated with sputum microscopy smear positivity. Researchers such as Miriam Brailey, Edith Lincoln and Jay Arthur Myers carried out studies, over three decades in some cases, documenting likely consequences of tuberculous infection in childhood at different ages and under different circumstances. Infected children aged <3 years remain candidates for the urgent institution of chemoprophylaxis and the search for close household contacts. In high-income communities with low TB incidence, a tuberculin-positive child remains an important index for the presence of infectious adults. Wade Hampton Frost drew attention to the age-related epidemiology of TB, identifying it as a most important feature of our understanding of TB pathophysiology; more than 70 years after his death, we still do not understand why there is a change in the nature of TB during adolescence that makes expectoration of infectious sputum possible.