Our search for new triapnosomaticidal drugs have an special  emphasis on those causing mitochondrial dysfunction, as oxidative phosphorylation contributed most to the bioenergetic requirements of the parasite. Drug modification to improve its accumulation in mitochondria. Assessment of inhibition of mitochondrial functionality and definition of their site of action by functional and enzymatic assays, molecular docking and lately, metabolomics. Mitochondrial targets for musalanone, sitamaquine, miltefosine, 14-hydroxylunularin and styrylquinolines have been achieved