Since the first reports of fetal alcohol syndrome (FAS), thousands of studies have examined the effects of antenatal alcohol exposure in humans and in animal models. Research with animal models has led to discoveries which would be difficult if not impossible in human subjects. Most importantly, these models have resulted in valuable insights into the actions of alcohol on various parts of the developing embryo and have helped researchers come closer to identifying the mechanisms of its teratogenic action. Both the direct and indirect biological effects of alcohol exposure in utero appear to work in conjunction with other concurrent and predisposing factors such as genotype, nutritional status, pattern of exposure and use of other drugs such as nicotine and cocaine. At present animal research indicates a multifactorial mechanism of the teratogenicity of alcohol resulting from nutrient deficiencies, fetal hypoxia and alterations in enzyme activities and cell function important in cell division and membrane integrity. This review examines how animal models are used to clarify issues associated with alcohol-related birth defects and to shed light on the underlying mechanisms.