Species differences are a major obstacle in predicting toxicity of xenobiotics from one species to another. Species differences in toxicity of drugs and other chemicals may be due to differences in pharmacokinetics or pharmacodynamics. This paper illustrates the point that species differences in pharmacokinetics of xenobiotics may be the result of differences in any of the processes contributing to the disposition of a xenobiotic. This is an important point because biotransformation as a cause of species differences for the disposition of xenobiotics has been overemphasized in the past, whereas only scant attention has been paid to the other 3 major contributing processes to disposition, viz. absorption, distribution, and excretion. This brief overview presents a balanced examination of all 4 major processes (absorption, distribution, biotransformation and excretion) as they affect the pharmacokinetics of xenobiotics in various species.