In this "Grand Challenges" paper, we review how the carbon isotopic composition of atmospheric CO 2 has changed since the Industrial Revolution due to human activities and their influence on the natural carbon cycle, and we provide new estimates of possible future changes for a range of scenarios. Emissions of CO 2 from fossil fuel combustion and land use change reduce the ratio of 13 C/ 12 C in atmospheric CO 2 (δ 13 CO 2). This is because 12 C is preferentially assimilated during photosynthesis and δ 13 C in plant-derived carbon in terrestrial ecosystems and fossil fuels is lower than atmospheric δ 13 CO 2. Emissions of CO 2 from fossil fuel combustion also reduce the ratio of 14 C/C in atmospheric CO 2 (Δ 14 CO 2) because 14 C is absent in million-year-old fossil fuels, which have been stored for much longer than the radioactive decay time of 14 C. Atmospheric Δ 14 CO 2 rapidly increased in the 1950s to 1960s because of 14 C produced during nuclear bomb testing. The resulting trends in δ 13 C and Δ 14 C in atmospheric CO 2 are influenced not only by these human emissions but also by natural carbon exchanges that mix carbon between the atmosphere and ocean and terrestrial ecosystems. This mixing caused Δ 14 CO 2 to return toward preindustrial levels in the first few decades after the spike from nuclear testing. More recently, as the bomb 14 C excess is now mostly well mixed with the decadally overturning carbon reservoirs, fossil fuel emissions have become the main factor driving further decreases in atmospheric Δ 14 CO 2. For δ 13 CO 2 , in addition to exchanges between reservoirs, the extent to which 12 C is preferentially assimilated during photosynthesis appears to have increased, slowing down the recent δ 13 CO 2 trend slightly. A new compilation of ice core and flask δ 13 CO 2 observations indicates that the decline in δ 13 CO 2 since the preindustrial period is less than some prior estimates, which may have incorporated artifacts owing to offsets from different laboratories' measurements. Atmospheric observations of δ 13 CO 2 have been used to investigate carbon fluxes and the functioning of plants, and they are used for comparison with δ 13 C in other materials such as tree rings. Atmospheric observations of Δ 14 CO 2 have been used to quantify the rate of air-sea gas exchange and ocean circulation, and the rate of net primary production and the turnover time of carbon in plant material and soils. Atmospheric observations of Δ 14 CO 2 are also used for comparison with Δ 14 C in other materials in many fields such as archaeology, forensics, and physiology. Another major application is the assessment of regional emissions of CO 2 from fossil fuel combustion using Δ 14 CO 2 observations and models. In the future, δ 13 CO 2 and Δ 14 CO 2 will continue to change. The sign and magnitude of the changes are mainly determined by global fossil fuel emissions. We present here simulations of future δ 13 CO 2 and Δ 14 CO 2 for six scenarios based on the shared socioeconomic pathways (SSPs) from the 6th Coupled Model...