**Abstract**

Malaria is a global public health issue. Despite the efforts in malaria prevention, nearly half the world's population is at risk of infection. Until present-day, researchers are struggling to design and discover an efficacious antimalarial. In comparison to most common antimalarial chemotypes that eliminate erythrocytic stages of *P. falciparum*, 4(1*H*)-quinolones and 4(1*H*)-pyridones exhibit antimalarial activity against multiple stages of the parasite. They have potential to treat blood stages of multidrug resistant *P. falciparum* malaria, eradicate dormant exoerythro stages of relapsing malaria species (*P. vivax*), and prevent transmission of infectious gametocytes to mosquitoes. However, thus far, the advancement of these chemotypes towards pre-clinical and clinical development has been impeded due to poor physicochemical properties, poor oral bioavailability, and poor dose-proportionality limiting preclinical safety and toxicity studies. Despite all these challenges, 4(1*H*) quinolones and 4(1*H*)-pyridones continue to be at the forefront for the development of the next-generation antimalarials as they would have tremendous global public health impact and could significantly enhance current malaria elimination efforts.

**Keywords:** 4(1*H*)-quinolones, 4(1*H*)-pyridones, malaria, resistance, plasmodium, antimalarials
