Metabolism of artemisinin derivatives, which are antimalarial sesquiterpenes, appeared to lead to the production of the more polar metabolites in general. Presence of the endoperoxide moiety in the A/B ring structure seems crucial for the expression of antimalarial activity of these compounds. Microbial models served as effective predictors for the mammalian metabolism of artemisinin derivatives as well as producing quantities of metabolites for reference standards and structure elucidation studies. Combination of 2D-NMR and Thermospray HPLC/MS techniques was very useful for the structure elucidation of metabolites.