Electron microscopy may be useful in chemotherapy studies at distinct levels, such as the identification of subcellular targets in the parasites and the elucidation of the ultimate drug mechanism of action, inferred by the alterations induced by antiparasitic compounds. In this review we present data obtained by electron microscopy approaches of different parasitic protozoa, such as Trypanosoma cruzi, Leishmania spp., Giardia lamblia and trichomonads, under the action of drugs, demonstrating that the cell architecture organization is only determined in detail at the ultrastructural level. The transmission electron microscopy may shed light (i.e. electrons) not only on the affected compartment, but also on the manner it is altered, which may indicate presumable target metabolic pathways as well as the actual toxic or lethal effects of a drug. Cytochemical and analytical techniques can provide valuable information on the composition of the altered cell compartment, permitting the bona fide identification of the drug target and a detailed understanding of the mechanism underneath its effect. Scanning electron microscopy permits the recognition of the drug-induced alterations on parasite surface and topography. Such observations may reveal cytokinetic dysfunctions or membrane lesions not detected by other approaches. In this context, electron microscopy techniques comprise valuable tools in chemotherapy studies.