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These parasites possess metabolic pathways that are divergent from those of their mammalian hosts and are often considered to be good targets for drug development. Sulfur-containing-amino-acid metabolism represents one such divergent metabolic pathway, namely, the cysteine biosynthetic pathway and methionine \u03b3-lyase-mediated catabolism of sulfur-containing amino acids, which are present in<jats:italic>T. vaginalis<\/jats:italic>and<jats:italic>E. histolytica<\/jats:italic>but absent in<jats:italic>G. intestinalis<\/jats:italic>. These pathways are potentially exploitable for development of drugs against amoebiasis and trichomoniasis. For instance,<jats:sc>l<\/jats:sc>-trifluoromethionine, which is catalyzed by methionine \u03b3-lyase and produces a toxic product, is effective against<jats:italic>T. vaginalis<\/jats:italic>and<jats:italic>E. histolytica<\/jats:italic>parasites in vitro and in vivo and may represent a good lead compound. In this review, we summarize the biology of these microaerophilic parasites, their clinical manifestation and epidemiology of disease, chemotherapeutics, the modes of action of representative drugs, and problems related to these drugs, including drug resistance. 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