Malaria is a vector-borne infectious disease caused by distinct species of a single-celled parasite called Plasmodium sp. However, an infected adult female Anopheles sp. mosquito that feeds on blood is responsible for the transmission of malaria. In the year 2020, approximately 241 million malaria cases and 627 thousand malaria deaths were recorded globally. In most tropical and subtropical regions of the world, malaria is one of the leading causes of death. Its transmission cuts across 86 countries with African continent recording approximately 95% deaths in 2020. Africa is mostly affected due to its weather conditions that support the easy spread of Plasmodium falciparum. Over time, relevant interventions have been made by researchers in the diagnosis, prevention, and treatment of malaria. Nevertheless, there are still challenges to its treatment and management globally. This review article is focused on the therapeutic intervention on malaria globally. Thus, published primary literatures reporting several relevant and new therapeutic interventions in malaria, as globally attained in the past years were collated and vital information critically reviewed. It is important to note that, the risk of contracting malaria is dependent on the region visited, length of stay, immunity, exposure and compliance with prophylaxis. Hence, to select treatment best suitable as a first-line therapy, combination antimalarial therapy, which consists of two or more antimalarial agents with different mechanisms of action was introduced and has been widely accepted and endorsed to prevent the development of drug resistance. Yet, immunization still remains the best measure for the eradication of malaria.