Abstract. Isoprene and its oxidation products are major players in the oxidative chemistry of the troposphere. Current understanding of the factors controlling biogenic isoprene emissions and of the fate of isoprene oxidation products in the atmosphere has been evolving rapidly. We use a climate–biosphere–chemistry modeling framework to evaluate the sensitivity of estimates of the tropospheric oxidative capacity to uncertainties in isoprene emissions and photochemistry. Our work focuses on two climate transitions: from the Last Glacial Maximum (LGM, 19 000–23 000 years BP) to the preindustrial (1770s) and from the preindustrial to the present day (1990s). We find that different oxidants have different sensitivities to the uncertainties tested in this study. Ozone is relatively insensitive, whereas OH is the most sensitive: changes in the global mean OH levels for the LGM-to-preindustrial transition range between −29 and +7 % and those for the preindustrial-to-present-day transition range between −8 and +17 % across our simulations. We find little variability in the implied relative LGM–preindustrial difference in methane emissions with respect to the uncertainties tested in this study. Conversely, estimates of the preindustrial-to-present-day and LGM-to-preindustrial changes in the global burden of secondary organic aerosol (SOA) are highly sensitive. We show that the linear relationship between tropospheric mean OH and tropospheric mean ozone photolysis rates, water vapor, and total emissions of NOx and reactive carbon – first reported in Murray et al. (2014) – does not hold across all periods with the new isoprene photochemistry mechanism. This study demonstrates how inadequacies in our current understanding of isoprene emissions and photochemistry impede our ability to constrain the oxidative capacities of the present and past atmospheres, its controlling factors, and the radiative forcing of some short-lived species such as SOA over time.