Testing of xenobiotics, food additives and supplements for potential developmental toxicity is performed according to regulatory study designs typically executed in pregnant rodents or rabbits and extrapolated to humans in the risk assessment process. One issue that often complicates the interpretation of such studies is the possibility that toxic effects on the maternal animal may secondarily cause adverse effects in the developing conceptus; such that developmental toxicity only occurs at doses also causing maternal toxicity. This chapter reviews maternal factors which may bear directly or indirectly on developmental outcome, with emphasis on those of greatest relevance to the risk assessment process. Standard teratology testing protocols call for top dosage levels that induce overt maternal toxicity, and the developmental effects of this toxicity (both alone, and with concurrent embryo/fetal insult) continue to present regulators with considerable interpretive difficulties. In response to these problems, there have been both research and literature review efforts concerning the relationship between maternal and developmental toxicity. Maternally mediated developmental toxicity has been shown to occur with a number of agents; further; toxicant-induced alterations in maternal physiology may affect the conceptus at dosages not causing overt maternal toxicity. The regulatory interpretation of maternal toxicity by regulatory bodies, and examples of studies undertaken with the aim of demonstrating that developmental effects are secondary to maternal toxicity or some alteration in maternal physiology will be presented.