Malaria is a major cause of mortality and morbidity globally. Great efforts have been made in the prevention and the elimination of malaria, especially in controlling the malaria vector, the mosquito. Another promising approach would be the development of malaria vaccines. Malaria vaccine studies can be focused on the pre-erythrocytic-stage antigens and the blood-stage antigens, and on the transmission blocking agents targeting the malaria gametocytes. The blood-stage antigens are the leading candidates in malaria vaccine development, as the blood-stage parasites are responsible for causing symptomatic malaria. Human acquired immunity largely targets on blood-stage antigens. This review focuses on one of the most extensively studied blood-stage antigen, the merozoite surface protein-1 (MSP-1), specifically on its evaluation and immunogenicity in rodents and primate models, and its safety and immunogenicity in human clinical trials.