The stomatal response to CO2 is important in understanding stomatal physiology, and important in understanding vegetation-atmosphere exchanges at all scales from the individual plant up to global vegetation. Despite the long history of experiments on stomatal responses to CO2 there are still considerable uncertainties in both these tasks. The difficulty in understanding differences in stomatal conductance between plants grown for any length of time in different CO2 atmospheres is stressed because of the many other possible changes in the plants' carbohydrate, nutrient and water relations. The other key issues that are highlighted are: whether stomata acclimate to CO2 either in parallel with any mesophyll photosynthetic acclimation or independently of changes in the mesophyll; whether stomata on different leaf surfaces respond to CO2 similarly; and whether reported changes in stomatal frequency are important to leaf gas exchange. The need for direct examination of stomatal sensitivity of plants grown in different CO2 concentrations is stressed.