Reprogramming of differentiated cells to induced pluripotent stem cells is a step-wise process of transcriptional changes. Here, we demonstrate that reprogramming signals can be biphasic, using the Wnt pathway as an example. The data point to opposing effects of Wnt signaling and its downstream regulators, the Tcf proteins, early and late in the reprogramming process, indicating that events promoting one phase can be inhibitory for a subsequent phase. These observations should encourage the development of dynamic reprogramming approaches.