Sulfur-containing amino acids play indispensable roles in a wide variety of biological activities including protein synthesis, methylation, and biosynthesis of polyamines and glutathione. Biosynthesis and catabolism of these amino acids need to be carefully regulated to achieve the requirement of the above-mentioned activities and also to eliminate toxicity attributable to the amino acids. Genome-wide analyses of enzymes involved in the metabolic pathways of sulfur-containing amino acids, including transsulfuration, sulfur assimilatory de novo cysteine biosynthesis, methionine cycle, and degradation, using genome databases available from a variety of parasitic protozoa, reveal remarkable diversity between protozoan parasites and their mammalian hosts. Thus, the sulfur-containing amino acid metabolic pathways are a rational target for the development of novel chemotherapeutic and prophylactic agents against diseases caused by protozoan parasites. These pathways also demonstrate notable heterogeneity among parasites, suggesting that the metabolism of sulfur-containing amino acids reflects the diversity of parasitism among parasite species, and probably influences their biology and pathophysiology such as virulence competence and stress defense.