Artemisinin derivatives are well tolerated in human, although there have been reported cases of mild gastrointestinal and neurological disorders. Their neurotoxicity is known but polyneuropathy induced by atemether-lumefantrine is debated. We report two cases of polyneuropathy due to arthmether-lumefantrine. These polyneuropathies are characterized by muscular disorders such as flask paralysis without superficial sensitivity disorders. For high doses, dihydroartemisinin, the active metabilite seems neurotoxic in animals according to the litterature. The seriousness and time of onset are dose-dependent. Nevertheless, the neurological effect of lumefantrine seems rare. In both cases, the causality assessment of arthmether-lumefantrine is probable according to the Naranjo probability score. The associated factors were misuse, self-medication, treatment without any parasitological evidence, and patient's predisposition. This report does not question the benefit /risk ratio of this drug which remains largely positive. These cases provide insight to the discussion regarding tolerance of Artemisinin-based Combination Therapy (ACT).