The search for agents useful for the prevention or cure of the protozoal diseases malaria and sleeping sickness was closely linked to the early development of medicinal chemistry (see Chapter 1). Unlike antibacterial agents, for which a few chemical structural classes exhibit a wide spectrum of biological activity, antiprotozoal activity exists in a wide variety of chemical classes, each of which possesses only a narrow chemotherapeutic spectrum. Antiprotozoal agents may be usefully subdivided into three broad categories: organometallics, carbocyclics, and heterocyclics. Each category may in turn be further subdivided on the basis of structural similarities among its members. The members of each group and subgroup as well as the protozoal genera against which each is currently used are outlined in the following section. Detailed descriptions of each compound (by number) are given in Section 3.