Caffeine, a component of coffee, soft drinks and chocolate, is widely consumed and considered harmless, although it has powerful effects on a variety of organs, systems and behavior. Caffeine, in typical concentration ranges of human consumption, acts as a non-specific blocker of the adenosine receptor. Caffeine molecules cross freely biological barriers, reaching the fetus during the entire gestation and it can be found in breast milk, reaching breastfeeding neonates. The exposure of fetus to caffeine and its metabolites depends on maternal caffeine metabolism, which shows marked genetic and environmental variation. Caffeine has been indicated as a cause of spontaneous abortion, intrauterine growth restriction, low birth weight, preterm delivery and decrease in fecundability. However, little or no reproductive adversity has been consistently associated with caffeine consumption. The pre-exposure of caffeine and the susceptibility to other drugs have been investigated considering the common intracellular way shared between them.