We explore the potential role of atmospheric carbon dioxide (CO 2 ) on isoprene emissions using a global coupled land-atmosphere model [Community Atmospheric Model-Community Land Model (CAM-CLM)] for recent (year 2000, 365 ppm CO 2 ) and future (year 2100, 717 ppm CO 2 ) conditions. We incorporate an empirical model of observed isoprene emissions response to both ambient CO 2 concentrations in the long-term growth environment and short-term changes in intercellular CO 2 concentrations into the MEGAN biogenic emission model embedded within the CLM. Accounting for CO 2 inhibition has little impact on predictions of present-day global isoprene emission (increase from 508 to 523 Tg C yr À1 ). However, the large increases in future isoprene emissions typically predicted in models, which are due to a projected warmer climate, are entirely offset by including the CO 2 effects. Projected global isoprene emissions in 2100 drop from 696 to 479 Tg C yr À1 when this effect is included, maintaining future isoprene sources at levels similar to present day. The isoprene emission response to CO 2 is dominated by the long-term growth environment effect, with modulations of 10% or less due to the variability in intercellular CO 2 concentration. As a result, perturbations to isoprene emissions associated with changes in ambient CO 2 are largely aseasonal, with little diurnal variability. Future isoprene emissions increase by more than a factor of two in 2100 (to 1242 Tg C yr À1 ) when projected changes in vegetation distribution and leaf area density are included. Changing land cover and the role of nutrient limitation on CO 2 fertilization therefore remain the largest source of uncertainty in isoprene emission prediction. Although future projections suggest a compensatory balance between the effects of temperature and CO 2 on isoprene emission, the enhancement of isoprene emission due to lower ambient CO 2 concentrations did not compensate for the effect of cooler temperatures over the last 400 thousand years of the geologic record (including the Last Glacial Maximum).