Pregnancy is a dynamic process, and maternal as well as fetal risks from cocaine use in pregnancy may differ as pregnancy progresses. Three areas of biology offer opportunities for reevaluating cocaine's effects in pregnancy: (1) Maternal cardiovascular and neurologic responses to cocaine hydrochloride are enhanced when compared with responses in nonpregnant subjects to the same dose per kilogram or to metabolites of crack cocaine. (2) During first trimester placental implantation, oxygen availability to the fetus may normally be limited. Cocaine-induced uterine artery vasoconstriction may lead to reperfusion and oxygen toxicity to the fetus from released reactive oxygen species. (3) Cocaine transport in the first and early second trimester may, in part, be across the placental chorion-amnion. Lacking a skin barrier, the fetus at mid-pregnancy may come in direct contact with high concentrations of cocaine in amniotic fluid, a reservoir that clears cocaine slowly, thereby prolonging exposure during critical periods of fetal neurotransmitter formation. Exploring these three areas of biology may offer new approaches to understanding the ultimate impact of prenatal cocaine exposure on maternal and fetal biology.