Photosynthesis depends on the diffusion of gaseous CO2 inside the leaf spaces from the stomatal entry point to the mesophyll cell walls. Although most research considers only the vertical diffusion from stomata on upper and/or leaf lower surfaces, some of the gas will diffuse in the lateral (paradermal) direction. The importance of lateral CO2 diffusion is reviewed, and the anatomical characteristics of leaves, including the variation of air space volume between species and conditions are discussed. The contribution of the air space conductance to the limitation of photosynthesis by the overall CO2 diffusion pathway is usually ignored. However, the need to consider three-dimensional diffusion at the small scale of a few stomata is emphasized because stomata are discrete, and separated by 20–300 µm. At the large scale of 100s of micrometres, there may be barriers to CO2 caused by the vascular tissue, particularly if there are bundle sheath extensions. The possible extent and controls on CO2 lateral and vertical diffusion in different species and conditions are illustrated using chlorophyll a fluorescence imaging techniques. It is clear that there is a range of effective lateral permeabilities depending on the particular vascular patterns and cell arrangements, and that species cannot be simply divided into homobaric and heterobaric anatomies. Lateral diffusion in more permeable leaves can be sufficient to affect measurements of leaf gas exchange, particularly when fluxes are low, although its contribution to leaf photosynthesis in natural conditions needs clarification.