The cellular plasma membrane contains enzymes whose active sites face the external medium rather than the cytoplasm. The activities of these enzymes, referred to as ecto-enzymes, can be measured using living cells. Ecto-phosphatases are ecto-enzymes that presumably hydrolyze extracellular phosphorylated substrates, releasing free inorganic phosphate. Although, several alternative functions have been suggested for these enzymes, such as participation in proliferation, differentiation, adhesion, virulence, and infection, little is known about the physiological roles of these enzymes in protozoa parasites. In this review, we discuss the principal features of ecto-phosphatases in protozoan parasites that are causative agents of important diseases such as Chagas' disease, leishmaniasis, amoebiasis, giardiasis, trichomoniasis and, sleeping sickness.