Malaria is an infectious disease. Many anti-malarial drugs have been introduced to eliminate malaria. Earlier, the major antimalarial drugs were natural products but in due course synthetic drugs have replaced them. Pursuing multiple strategies is needed for discovering new drugs for malaria. Global International Centers of Excellence for Malaria Research (ICEMR) network is conducting many research studies. The research activities include clinical studies for assessing antimalarial drug efficacies, drug susceptibilities of parasite isolates and determining resistancemediating parasite polymorphisms. There are several approaches for the discovery of new drugs. The approaches should also focus on low cost and novel therapies. Currently, the available drugs are optimized in many ways using combination therapy and the discovery of compounds from plants. This chapter focuses on the available antimalarial medications, including both synthetic and natural products. The present chapter also highlights indigenous medicinal plants, which can be potentially used for the development of antimalarial drugs.