Waddington’s epigenetic landscape metaphor (1957) describes development as a ball rolling down an uneven, sloping surface. In this picture, branching valleys represent different cell fates. John B. Gurdon’s nuclear transplantation experiments (1960, 1962) later challenged the notion that differentiation is strictly one-way. Gurdon showed that nuclei from fully differentiated Xenopus cells can, under the right conditions, revert to a pluripotent state and give rise to whole tadpoles. In this lecture, we will discuss what Gurdon’s findings reveal about the nature of cellular differentiation and how his research influenced later studies on cellular reprogramming.