In both plants and animals, cell-to-cell signaling controls key aspects of development. In plants, cells communicate through direct transfer of transcription factors between cells. It is thought that most, if not all, mobile transcription factors move via plasmodesmata, membrane-lined channels that connect nearly all cells in the plant. However, the mechanisms by which these proteins access the plasmodesmata are not known. Using four independent assays, we examined the movement of the SHORT-ROOT (SHR) transcription factor under conditions that affect microtubule stability, organization or dynamics. We found that intact microtubules are required for cell-to-cell trafficking of SHR. Either chemical or genetic disruption of microtubules results in a significant reduction in SHR transport. Interestingly, inhibition of microtubules also results in mis-localization of the SHR-INTERACTING EMBRYONIC LETHAL (SIEL) protein, which has been shown to bind directly to SHR and is required for SHR movement. These results show that microtubules facilitate cell-to-cell transport of an endogenous plant protein.