The construction of a secondary cell wall is an important and necessary developmental decision that supports cell function and plant stature. Unlike the primary cell walls, which are initiated during cell division and develop along with the expansion of the cells, secondary cell walls are constructed after the cells have stopped growing. Hence, the transition from primary to secondary wall synthesis marks an important and distinct metabolic investment by the plant. This transition requires a coordinated change of a plethora of cellular processes, including hormonal, transcriptional and post-transcriptional activities, metabolic flux re-distributions and enzymatic activities. In this review, we briefly summarize the hormonal and transcriptional control of the primary to secondary wall transition, and highlight important gaps in our understanding of the metabolic framework that support the transition. Several tools that may aid in future research efforts to better understand the changes in cell wall synthesis during the trans-differentiation are also discussed.