In this short communication, we have discussed about killer disease malaria and drug resistance caused by many popular drugs. Malaria is oldest and very important parasitic disease in mankind from ancient times. Millions of people are at high risk of this disease every year. This disease has become major cause of morbidity and mortality in this world because of emergence of resistance to first line drugs. Because of development of resistance of old drug molecules and therapies, WHO recommends combination therapies for the treatment of malaria. This short communication will highlight the reason of resistance along with new findings of molecules against resistance developed molecules in the market. Artemisinin combination therapies are first line treatment for all Plasmodium falciparum parasites in malaria endemic countries of the world according to WHO recommendations. Malaria eradication will become a battle in the world with urgent need of new drug molecule or therapy to combat against this disease leading to effective global malaria control programme.