Isoprene is the dominant volatile organic compound produced by the terrestrial biosphere and fundamental for atmospheric composition and climate. It constrains the concentration of tropospheric oxidants, affecting the lifetime of other reduced species such as methane and contributing to ozone production. Oxidation products of isoprene contribute to aerosol growth. Recent consensus holds that emissions were low during glacial periods (helping to explain low methane concentrations), while high emissions (contributing to high ozone concentrations) can be expected in a greenhouse world, due to positive relationships with temperature and terrestrial productivity. However, this response is offset when the recently demonstrated inhibition of leaf isoprene emissions by increasing atmospheric CO2 concentration is accounted for in a process-based model. Thus, isoprene may play a small role in determining pre-industrial tropospheric OH concentration and glacial-interglacial methane trends, while predictions of high future tropospheric O3 concentrations partly driven by isoprene emissions may need to be revised.