Lack of approved pharmaceutical agents and very limited pharmacokinetic data in the scientific literature for exotic, wildlife, and zoo species are a major issue for veterinarians treating these species. There are fewer than 15 compounds approved in the United States for zoo and wildlife species compared to nearly 300 drugs licensed for cattle. Zoo veterinarians are therefore required to extrapolate the use of approved agents (veterinary or human) to nonapproved species, often with little or no scientific basis to support drug or dose schedule selection. In general, species differences in drug absorption, metabolism, distribution, and excretion have been well documented for domestic species. However, there has been limited research to provide similar data for nondomestic species. Consequently, with the possible exception of pet bird species, there is little published information on the pharmacokinetic parameters of drugs in nondomestic species. Additionally, because of the commercial value of many zoo species, the traditional method of "trial and error" for drug and dose selection and related compliance issues is often inappropriate. There is an understandable concern, whereby the zoo veterinarian does not wish to be the first to administer an agent or formulation in an untested species. "One medicine" is a central concept in treating zoo species, in that vertebrate species are generally more similar than dissimilar. However, drug absorption can vary within as well as between species. Considering the anatomical differences between true monogastrics (canine and feline species), hind-gut fermentors (rodents, rabbits, horses, and elephants), fore-gut fermentors (Colobus monkeys and kangaroos), and ruminants (cattle, goats, sheep, and antelope), the potential for differences in pharmacokinetic profiles are marked. Moreover, there are potential differences between organisms in a single class. An example is the ability of several snake species to up- and down-regulate their digestive systems. This renders the time course of oral drug absorption dependent on both body temperature and time after feeding. Plasma protein binding may vary considerably between species and may also be temperature dependent. This is very significant when treating poikilothermic (reptiles, amphibians, and fish) species and when conducting pharmacokinetic studies with highly protein-bound drugs. The large body sizes of some zoo species create additional considerations for treatment with drugs and can place significant limitations on delivery of an effective drug dose.