From ancient times until 21st century, Malaria has remained a fatal disease. It causes death in many poor and developing countries. Excluding vector control, Antimalarial drugs are the most reliable and effective weapon to tackle this severe disease. The emergence of antimalarial drug resistance in Plasmodium spp. becomes a barrier in Malaria elimination program as there has been no effective antimalarial vaccine till today. Apart from artemisinin, most of the antimalarial drugs have become resistant against malaria at present. Although, reduced efficacy of artemisinin-based combination therapy (ACT) has also been reported from southeast regions of Asia. Mutation of some genes within the parasite play a vital role in this drug resistance. Therefore, malaria is still a prime threat to human death and an unsolved problem. Newly emerging approaches like, vaccine development, plants based antimalarial drugs, nanoparticles, next generation antimalarial drugs should be taken & supported. In addition to that, public awareness is much needed for understanding the fatality of the disease and for encouraging self-protection and early treatment.