In Tanzania, malaria remains one of the major causes of illness and death. The disease causes major obstacles to social and economic development. The extent of the problem is greatest among children less than five years of age and pregnant women. Malaria has been estimated to cost Tanzania more than US$ 240 million every year in lost gross domestic product, although it can be controlled for a fraction of that sum. Tanzania has actively participated in malaria research and in developing most control tools. However, the use of such tools and scaling up of effective interventions has been a major challenge. Major system constraints include inadequate human, financial, material resources, as well as an inefficient health care system. With an increasing burden with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), there has been a shift in the use of resources whereby more prioritization is given to interventions for HIV/AIDS than for malaria. The country is faced with several challenges including diagnosis, treatment, and control measures. Districts are faced with the inability to generate reliable information needed to make decisions to inform policy and lack skills for priority setting and planning. Budget allocation is not done according to evidence-based priorities, thus leading to stagnation over time. In this report, we present some success stories and discuss the challenges facing scaling up of interventions and propose priority areas to solving the problems.