The quest for an effective vaccine as an additional strategy in the control of malaria and to significantly impact the disease burden has progressed tremendously over the past decade and there is a very high probability that a malaria vaccine will be available for use in the near future. The development and deployment of an effective malaria vaccine faces several challenges and the early engagement of endemic country institutions in the entire process will be beneficial to all. It is very likely that the initial vaccine candidates will have to be improved upon, especially as our understanding of the disease processes improves and the number of potential vaccine antigens increase. This will place greater demands on the currently insufficient capacity for trials. Current strategies for testing and deployment of a malaria vaccine, for example those focusing on risk groups such as infants and children and pregnant women, will also need modifications as efforts are moved towards malaria elimination. Also, a successful malaria vaccine development process will need strengthening of the currently weak regulatory framework in endemic countries to enable them have oversight over clinical trials. The introduction of any malaria vaccine will be confronted by some cultural issues and it is essential to understand how these factors will ultimately affect its utilization. These and other challenges related to the development and deployment of an effective malaria vaccine especially as they concern endemic countries are discussed.