Plants need to develop thickened cell walls with appropriate localization through precise regulation during the process of growth and development in order to support their body weight and to build long distance transportation systems. Wall thickening is achieved through a multitude of regulatory networks in various tissues under changeable environments. In this mini-review, we summarize current understanding of the regulatory pathways and mechanisms involved in cell wall thickening. Regulation of cell wall thickening is not only mechanistically essential to understand the plant structure accretion but also has applicable significance to plant cell wall biomass utilization.