Respiratory illness is the major cause of mortality and morbidity in African children. The spectrum of disease includes acute and chronic respiratory illness. As a result of the HIV epidemic currently occurring in sub-Saharan Africa, HIV-associated acute and chronic respiratory disease has emerged as a major factor in the epidemiology of childhood respiratory illness. Pneumonia is the leading causes of childhood mortality responsible for approximately 21% of deaths in African children under five years of age each year. The HIV pandemic has increased the incidence, severity and pneumonia mortality in African children. Pulmonary tuberculosis (TB) is an important cause of morbidity and death. Globally, the highest TB incidence rates occur in sub-Saharan African countries; many of these countries are also experiencing a dual HIV epidemic, resulting in an exponential increase in TB cases. The burden of childhood respiratory illness has necessitated novel and improved ways of diagnosis, treatment and prevention, particularly in the context of limited resources. Improved diagnosis, treatment and prevention of pneumonia have been a research focus, particularly in HIV-infected children. African studies have provided information on the epidemiology, aetiology and outcome from pneumonia in HIV-infected and uninfected children. The efficacy of trimethoprim-sulphamethoxazole prophylaxis in reducing mortality and morbidity in HIV-infected African children was shown in the only randomized controlled trial. Two large studies have shown the efficacy of the pneumococcal conjugate vaccine in an African context. Regarding TB, areas of research include diagnostic studies and improved preventative strategies. Promising diagnostic studies for childhood TB include the use of sputum induction, PCR techniques and blood interferon assays. The immune reconstitution inflammatory syndrome (IRIS) has emerged as a new clinical entity in HIV-infected children with TB associated with use of antiretroviral therapy. New preventative strategies for TB include novel vaccines and primary prophylaxis. Available, effective interventions for prevention and treatment of childhood respiratory disease exist; the challenge is to achieve widespread implementation and high coverage rates in African countries. Greater access to newer vaccines and, in HIV-infected children, to anti-retroviral therapy and prophylaxis is necessary to further reduce the burden of childhood respiratory illness in Africa.