Malaria is one of the major health problems in developing countries. It kills 1-2 million people every year and also it affects financial status of many countries. Developed resistance to aminoquinoline (chloroquine), quinoline methanols (Quinine, Mefloquine) created troubles in malarial chemotherapy and signs of appearance of resistance to artemisinin based combination therapy (ACT) created emergency to develop novel antimalarial agents with high efficacy before spreading of resistance to ACT. From the ages natural products played an important role in antimalarial therapy, identification of natural products, semisynthetic and synthetic analogs with potent antiplasmodium activity is one of the best methods to develop novel antimalarial agents. In this review, we are presenting the antimalarial activity of natural β-carboline alkaloids and special interest on manzamine alkaloids and their structure activity relationship.