In this review, an attempt has been made to summarize our current understanding of the mechanisms whereby certain chemicals cause birth defects. The chemicals selected for consideration were those that have been designated as established or recognized human teratogens. It is clear that our current understanding of mechanisms whereby these agents cause teratogenic effects (birth defects) can vary dramatically from one agent to the next. Extremes include the folic acid antagonists, which are now well established as agents that produce birth defects by virtue of potent inhibition of dihydrofolate reductase as a primary biochemical mechanism. An example at the other extreme is ethanol, for which very few definitive statements can be made with regard to teratogenic mechanisms, and the probability exists that a large number of interacting, contributory mechanisms can be invoked. For nearly all chemical teratogens, the critical links in the chains of events between the initial, primary biochemical and molecular mechanistic event (e.g. dihydrofolate reductase inhibition) and the manifestations of specific abnormalities (pathogenic mechanisms) remain to be delineated. This will provide an enormous challenge for investigators for years to come.