Malaria continued to be a deadly situation for the people of tropical and subtropical countries. Although there has been a marked reduction in new cases as well as mortality and morbidity rates in the last two decades, the reporting of malaria caused 247 million cases and 619000 deaths worldwide in 2021, according to the WHO (2022). The development of drug resistance and declining efficacy against most of the antimalarial drugs/combination in current clinical practice is a big challenge for the scientific community, and in the absence of an effective vaccine, the problem becomes worse. Experts from various research organizations worldwide are continuously working hard to stop this disaster by employing several strategies for the development of new antimalarial drugs/combinations. The current review focuses on the history of antimalarial drug discovery and the advantages, loopholes, and opportunities associated with the common strategies being followed for antimalarial drug development.