Malaria, caused by apicomplexan parasite, is an old disease and continues to be a major public health threat in many countries. This article aims to present different aspects of malaria including causes, pathogenesis, prevention, and treatment in an articulate and comprehensive manner. Six Plasmodium species are recognized as the etiology of human malaria, of which Plasmodium falciparum is popular in East and Southern Africa. Malaria is transmitted mainly through Anopheles gambiae and Anopheles funestus, the two most effective malaria vectors in the world. Half of the world’s population is at risk for malaria infection. Globally, the morbidity and mortality rates of malaria have become decreased even though few reports in Ethiopia showed high prevalence of malaria. The malaria parasite has a complex life cycle that takes place both inside the mosquito and human beings. Generally, diagnosis of malaria is classified into clinical and parasitological diagnoses. Lack of clear understanding on the overall biology of Plasmodium has created a challenge in an effort to develop new drugs, vaccines, and preventive methods against malaria. However, three types of vaccines and a lot of novel compounds are under perclinical and clinical studies that are triggered by the occurrence of resistance among commonly used drugs and insecticides. Antiadhesion adjunctive therapies are also under investigation in the laboratory. In addition to previously known targets for diagnostic tool, vaccine and drug discovery scientists from all corner of the world are in search of new targets and chemical entities.