Over the last two decades, Tanzania has registered improvement in the health status of the population and a reduction in the overall disease burden. However, the burden of communicable diseases and maternal and child health conditions, including nutrition, remains persistently high. These conditions can be prevented and treated with existing affordable and cost-effective interventions but remain major public health problems. Besides the persistently high burden of communicable diseases, Tanzania is witnessing a growing burden of non-communicable diseases (NCDs) and is at risk of a protracted, full-fledged double burden of disease. The study assessed the current and future trajectory of the disease burden, assessed the organization and performance of the health care delivery system in responding to the disease burden, and identified actions that Tanzania would need to employ to address the major causes of disease burden so that they may cease to be major public health problems.