One of the current options for reducing the morbidity and mortality of malaria are chemoprophylaxis and chemotherapy. For this reason, the increasing prevalence of strains of Plasmodium falciparum resistant to chloroquine and other antimalarial drugs poses a serious problem for control of malaria. There is an urgent need to find and develop novel compounds and to identify novel chemotherapeutic targets. Different approaches to discover new compounds are presented from examples of molecules studied in the Tropical Medicine Institute of the French Army Health Service (IMTSSA) evaluation against isolates of compounds in pharmaceutical development in collaboration with pharmaceuticals (pyronaridine, benflumetol, ferrochloroquine), screening of molecules which are still registered for other pathologies (antibiotics), screening of new synthesized compounds (artemisinin derivatives) and identification of parasitical targets and essential metabolic ways for parasite, and identification of molecules acting on these targets (reversal of resistance to chloroquine, iron chelators).