Malaria is a major global health problem, particularly in tropical and subtropical countries due to the development of resistance. Most deadly malaria infection is caused by Plasmodium falciparum. Heterocycles have played a significant role as leads in the design of antimalarial drugs since the characterization of quinine till date. The presence of heteroatom (s) in molecules ensures diverse target points and provides the functionalities to manipulate and generate more efficacious antimalarial drugs. This review looks at malaria disease: its transmission and host responses, analogue drug design strategy, identification of hits and leads in antimalarial drug discovery and recently developed antimalarial agents based on heterocycles.