Very accurate long-term measurements of atmospheric CO2 concentrationsbi are needed to understand the role of human activities on the greenhouse effect, as well as the interactions between anthropogenic emissions and the natural carbon cycle. Knowledge of the carbon cycle has been acquired through the development describes the development of atmospheric measurement networks and methods for measuring CO2 in the atmosphere, including the measurement of CO2 in air bubbles extracted from ice cores, the emergence of precise in situ measurements at the beginning of the 1960s, and the operational networks now deployed in certain parts of the world. The surface network of atmospheric stations where CO2 is measured, either in air samples or by in situ instrumentation, made up of about 150 monitoring sites, supplemented by airborne measurements on board of research and commercial aircrafts, is coordinated by international projects aimed at guaranteeing a long-term measurement compatibility to within approximately 0.025‰ (0.1 ppm). This level of accuracy is necessary to characterize atmospheric signals such as the long-term trend, which has risen in 60 years from 1 to 2.2 ppm/year, but also the interannual, seasonal, and regional variations of CO2. These atmospheric signals provide unique information about natural biogeochemical cycles and their current disturbance. The additional measurement of radiocarbon in atmospheric CO2, as described in this article, also makes it possible to identify the contribution due to fossil fuel CO2 emissions. The logistics and metrological requirements of in situ measurements mean that the monitoring network only covers the globe very incompletely—hence the importance of satellite observations, which have been developing strongly since their emergence in the early 2000s. Recent space-based CO2 observations make it possible to measure the concentration of CO2 averaged in the atmospheric column with global coverage under cloud-free conditions, providing millions of measurements each year, with a precision that can now reach 1 ppm, thus 10 times less than in situ instrumentation. Similar measurements of total CO2 columns are also made by ground-based remote sensing instruments, at about 100 sites over the world. They provide important reference data to evaluate atmospheric CO2 measurements from satellites and, in combination with in situ measurements of vertical profiles, provide a transfer standard between the satellite measurements and ground-based in situ networks. This article provides an overview of CO2 monitoring programs and what they tell about large-scale biogeochemical change. The perspectives for the development of CO2 observations are important both for surface networks and for space-based observations, with the objective of moving toward the characterization of processes at increasingly fine spatial scales, in particular toward urban emissions.