Observational studies suggest an adverse effect of maternal hypovitaminosis D during pregnancy. However, intervention studies failed to show convincing benefit from vitamin D supplementation during pregnancy. With analytical advances, vitamin D can now be measured in ten forms-including as epimers-which were thought to be biologically inactive, but can critically impair immunoassays. The aim of this commentary is to highlight the potential clinical and analytical significance of vitamin D epimers in the interpretation of vitamin D roles in pregnancy. Epimers may contribute a considerable proportion of total vitamin D-especially in the neonate-which renders the majority of common assays questionable. Furthermore, epimers have been suggested to have activity in laboratory studies, and evidence suggests that the fetus contributes significantly to epimer production. Maternal epimer levels contribute significantly to predict neonate circulating 25-hydroxyvitamin D concentrations. In conclusion, the existence of various vitamin D forms (such as epimers) has been established, and their clinical significance remains obscure. These results underscore the need for accurate measurements to appraise vitamin D status, in order to understand the current gap between observational and supplementation studies on the field.