The national scale-up of antiretroviral therapy (ART) in Malawi is based on a public health approach, with principles and practices borrowed from the successful DOTS (directly observed treatment short course—the system used to successfully deliver antituberculosis treatment to people in some of the poorest countries of the world) tuberculosis control framework. During the first 6 years, the number of patients registered on treatment increased from 3000 to >350,000 in both the public and private sectors. The most important reasons for this success have been strong international and national leadership combined with adequate funds, a standardized approach to ART with practical guidelines, an approved national scale-up plan with clear, time-bound milestones; investment in an intensive program of training and accreditation of ART sites, quarterly supervision and monitoring of ART and operational research, rational drug forecasting and no stock-outs of drugs during the first few years, and involvement of the private sector. The looming challenges of human resources, guaranteed financial support, better but also more expensive ART regimens, use of electronic medical records to monitor response to therapy, and attention to HIV prevention need to be met head-on and solved if the momentum of the earlier years is to be maintained.