PURPOSE OF REVIEW: We review recently published literature concerning early morbidity and mortality during antiretroviral therapy (ART) among patients in resource-limited settings. We focus on articles providing insights into this burden of disease and strategies to address it. RECENT FINDINGS: In sub-Saharan Africa, mortality rates during the first year of ART are very high (8-26%), with most deaths occurring in the first few months. This figure compares with 3-13% in programmes in Latin America and the Caribbean and 11-13% in south-east Asia. Risk factors generally reflect late presentation with advanced symptomatic disease. Key causes of morbidity and mortality include tuberculosis (TB), acute sepsis, cryptococcal meningitis, malignancy and wasting syndrome/chronic diarrhoea. Current literature shows that the fundamental need is for much earlier HIV diagnosis and initiation of ART. In addition, further studies provide data on the role of screening and prophylaxis against opportunistic diseases (particularly TB, bacterial sepsis and cryptococcal disease) and the management of specific opportunistic diseases and complications of ART. Effective and sustainable delivery of these interventions requires strengthening of programmes. SUMMARY: Strategies to address this disease burden should include earlier HIV diagnosis and ART initiation, screening and prophylaxis for opportunistic infections, optimized management of specific diseases and treatment complications, and programme strengthening.