One way to increase potential crop yield could be increasing mesophyll conductance gm. This variable determines the difference between the CO2 partial pressure in the intercellular air spaces (Ci) and that near Rubisco (Cc). Various methods can determine gm from gas exchange measurements, often combined with measurements of chlorophyll fluorescence or carbon isotope discrimination. gm lumps all biochemical and physical factors that cause the difference between Cc and Ci. gm appears to vary with Ci. This variability indicates that gm does not satisfy the physical definition of a conductance according to Fick's first law and is thus an apparent parameter. Uncertainty about the mechanisms that determine gm can be limited to some extent by using analytical models that partition gm into separate conductances. Such models are still only capable of describing the CO2 diffusion pathway to a limited extent, as they make implicit assumptions about the position of mitochondria in the cells, which affect the re-assimilation of (photo)respired CO2. Alternatively, reaction-diffusion models may be used. Rather than quantifying gm, these models explicitly account for factors that affect the efficiency of CO2 transport in the mesophyll. These models provide a better mechanistic description of the CO2 diffusion pathways than mesophyll conductance models. Therefore, we argue that reaction-diffusion models should be used as an alternative to mesophyll conductance models, in case the aim of such a study is to identify traits that can be improved to increase gm.