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The demographic and nutritional transitions taking place in Uganda, just as in other low- and middle-income countries (LMIC), are leading to accelerating growth of chronic, non-communicable diseases (NCDs). Though still sparse, locally derived data on NCDs in Uganda has increased greatly over the past five years and will soon be bolstered by the first nationally representative data set on NCDs. Using these available local data, we describe the landscape of the globally recognized major NCDs- cardiovascular disease, diabetes, cancer, and chronic respiratory disease- and closely examine what is known about other locally important chronic conditions. For example, mental health disorders, spawned by an extended civil war, and highly prevalent NCD risk factors such as excessive alcohol intake and road traffic accidents, warrant special attention in Uganda. Additionally, we explore public sector capacity to tackle NCDs, including Ministry of Health NCD financing and health facility and healthcare worker preparedness. Finally, we describe a number of promising initiatives that are addressing the Ugandan NCD epidemic. These include multi-sector partnerships focused on capacity building and health systems strengthening; a model civil society collaboration leading a regional coalition; and a novel alliance of parliamentarians lobbying for NCD policy. Lessons learned from the ongoing Ugandan experience will inform other LMIC, especially in sub-Saharan Africa, as they restructure their health systems to address the growing NCD epidemic.