Vitamin A and its derivatives, the retinoids, have been implicated as important signaling molecules in vertebrate development, primarily due to numerous gain-of-function experiments involving treatment of embryos with exogenous retinoic acid. Collectively, the results from these experiments suggested that retinoids were sufficient to mimic the action of endogenous factors which posteriorize the embryonic axis, however the question of their necessity has remained unclear. Recent loss-of-function experiments from several laboratories have shown that retinoids are indispensable for regionalizing the anteroposterior axis and promoting neuronal differentiation. These results firmly establish retinoids as endogenous signaling molecules that are required for embyronic patterning.