The 13C-depletion of plant organic matter compared to atmospheric CO2 has been known for more than half a century (Craig 1953, 1954), and it is now one of the most famous isotope fractionations in biology. In fact, photosynthesis fractionates between 12CO2 and 13CO2 so that plant CO2 fixation favors 12CO2 and plant organic matter and metabolites are 13C-depleted. The applications of carbon isotope fractionation by photosynthetic metabolic are numerous, and at the date of publication of the present chapter, as much as 29,000 papers involving the 12C/13C isotope fractionation in plantsC/C isotope fractionation in plants have been published. The consequences of the photosynthesis-driven fractionation are also visible at the ecosystem scale because the carbon input into trophic webs is generally 13C-depleted and thus directly impacts on all carbon compartments of the ecosystem. Since the 1980s, models have been developed to explain and predict the isotope composition (δ13C) of photosynthetic products and the fractionation associated with CO2 fixation, and they have been extremely successful in complementing gas exchange models to compute carbon balance at the leaf, ecosystem or global scale (Lloyd and Farquhar 1994; Aranibar et al. 2006; McDowell et al. 2008). Photosynthetic isotope fractionationPhotosynthetic isotope fractionation by plants (and phytoplankton) has global consequences since it contributes to the annual oscillations of the δ13C value in atmospheric CO2. In other words, the microscopic effects of isotopomer selection by photosynthetic mechanisms (diffusion, enzymes, etc.) have global consequences and this is now routinely exploited to compute the carbon budget of the Earth.