Amodiaquin is still considered as a poorly tolerated antimalarial causing hematological and hepatic toxicity. In view of complications observed during prophylaxis, the WHO has advised against the use of amodiaquin for prophylaxis as well as treatment. However due to the rapid increase in chloroquine resistance and to the absence of reported cases of toxicity during treatment, the WHO has reconsidered its position and now accepts therapeutic use of amodiaquin under some conditions. It has been demonstrated that amodiaquin activates release of quinoneimine granulocytes causing hematological toxicity. In liver microsomes, metabolism into desethyl derivatives is catalyzed by cytochrome P450 CYP2C8 that has several variant forms with low activity on amodiaquin clearance. Carriers of these variants are at a higher risk for adverse effects. Currently the safety and effectiveness of amodiaquin in association with artesunate has been documented and this therapeutic combination is now recommended for first line treatment of uncomplicated Plasmodium falciparum malaria in 18 African countries.