While the precise mode of action of artemisinin (ART) derivatives remains obscure, it is nonetheless commonly accepted that ART generates reactive oxygen intermediates that contribute to cell death. Also, numerous studies confirm that point mutations in the propeller domain of K13 protein play a key role in resistance to ART derivatives. Because of its homology with the KEAP1 protein, it is thought that this protein may have a role in the polyubiquitination of proteins and that its alteration may cause resistance of young parasite stages to the drug. In this chapter, we present our current knowledge of K13-related resistance to ART and its spread in Southeast Asia and discuss its possible emergence and/or diffusion in Africa.