There are many benefits of breast-feeding both for the infant and for the mother. Nursing mothers who are also taking medications or exposed to environmental hazards may be confronted with a difficult choice to discontinue nursing or maternal medication or risk potential harm to the infant. Frequently, these decisions are made without sufficient information or understanding of the factors influencing exposure. The current review explores two indices of exposure, together with their pharmacokinetic determinants. Both of the indices include the milk to serum (M/S) concentration ratio for a given drug and the volume of milk consumed. The first exposure term, EI(Dose), expresses neonatal dose as a percentage of maternal dose and is inversely related to the maternal systemic clearance. By contrast, the second exposure term, EI(Conc), expresses infant concentration as a percentage of maternal concentration and is inversely related to the infant systemic clearance. Issues related to intersubject variation in M/S (e.g., colostrum vs. mature milk, fore vs. hind milk) and infant clearance (e.g., ontogeny of elimination pathways, pharmacogenetics) and their role in modulating exposure are also discussed.