The key role of cell walls in setting mesophyll conductance to CO₂ (g_m) and, consequently, photosynthesis, is reviewed. First, the theoretical properties of cell walls that can affect g_m are presented. Then, we focus on cell wall thickness (T_cw) reviewing empirical evidence showing that T_cw varies strongly among species and phylogenetic groups in a way that correlates with g_m and photosynthesis i.e. the thicker the mesophyll cell walls, the lower g_m and photosynthesis. Potential interplays of g_m, T_cw, dehydration tolerance and hydraulic properties of leaves are also discussed. Dynamic variations of T_cw in response to the environment and their implications in the regulation of photosynthesis are discussed, and recent evidence suggesting an influence of cell wall composition on g_m are presented. We then propose a hypothetical mechanism for the influence of cell walls on photosynthesis, combining the effects of thickness and composition, particularly pectins. Finally, we discuss the prospects for using biotechnology for enhancing photosynthesis by means of altering cell wall-related genes.