We describe the development and analysis of a global model based on Model of Emissions of Gases and Aerosols from Nature (MEGAN) (Guenther et al., 2006) for estimating isoprene emissions from terrestrial vegetation. The sensitivity of calculated isoprene emissions to descriptors including leaf age, soil moisture, atmospheric CO2 concentration, and regional variability of emission factors is analyzed. The validity of the results is evaluated by comparison with compilations of published field-based canopy-scale observations. Calculated isoprene emissions reproduce above-canopy flux measurements and the site-to-site variability across a wide range of latitudes, with the model explaining 60% of the variance. Although the model underestimates isoprene emissions, especially in northern latitude localities, this disagreement is significantly corrected when regional variability of emission factors for particular plant functional types is considered (r(2) = 0.78). At the global scale, we estimate a terrestrial biosphere isoprene flux of 413 TgC yr(-1) using the present-day climate, atmospheric CO2 concentration, and vegetation distribution, and this compares with other published estimates from global modeling studies of 402 to 660 TgC yr(-1). The validated model was used to calculate changes in isoprene emissions in response to atmospheric CO2 increase, climate change, and land use change during the 20th century (1901-2002). Changes in all of these factors are found to impact significantly on isoprene emissions over the course of the 20th century. Between 1901 and 2002, we estimate that at the global scale, climate change was responsible for a 7% increase in isoprene emissions, and rising atmospheric CO2 caused a 21% reduction. However, by the end of the 20th century (2002), anthropogenic cropland expansion has the largest impact reducing isoprene emissions by 15%. Overall, these factors combined to cause a 24% decrease in global isoprene emissions during the 20th century. It remains to be determined whether predicted 21st century warming and increased use of isoprene-emitting crops for biofuels ( e. g., oil palm) will more than offset any future CO2 suppression of isoprene emission rates