The biochemical and molecular processes involved in the habituation of maize cells to growth in the presence of the cellulose biosynthesis inhibitor dichlobenil (DCB) were investigated. DCB affects the synthesis of cellulose both in active and stationary growth phases and alters the expression of several CesA genes. Of these, ZmCesA5 and ZmCesA7 seem to play a major role in habituating cells to growth in the presence of DCB. As a consequence of the reduction in cellulose, the expression of several genes involved in the synthesis of hydroxycinnamates is increased, resulting in cell walls with higher levels of ferulic and p-coumaric acids. A proteomic analysis revealed that habituation to DCB is linked to modifications in several metabolic pathways. Finally, habituated cells present a reduction in glutathione S-transferase detoxifying activity and antioxidant activities. Plant cell adaptation to the disturbance of such a crucial process as cellulose biosynthesis requires changes in several metabolic networks, in order to modify cell wall architecture and metabolism, and survive in the presence of the inhibitor. Some of these modifications are described in this paper.