Biogenic volatile organic compounds (BVOCs), primarily emitted by terrestrial vegetation, are highly reactive and have large effects on the oxidizing potential of the troposphere, air quality and climate. In terms of global emissions, isoprene is the most important BVOC. Droughts bring about changes in the surface emission of biogenic hydrocarbons mainly because plants suffer water stress. Past studies report that the current parameterization in the state-of-the-art Model of Emissions of Gases and Aerosols from Nature (MEGAN) v2.1, which is a function of the soil water content and the permanent wilting point, fails at representing the strong reduction in isoprene emissions observed in field measurements conducted during a severe drought. Since the current algorithm was originally developed based on potted plants, in this study, we update the parameterization in the light of recent ecosystem-scale measurements of isoprene conducted during natural droughts in the central U.S. at the Missouri Ozarks AmeriFlux (MOFLUX) site. The updated parameterization results in stronger reductions in isoprene emissions. Evaluation using satellite formaldehyde (HCHO), a proxy for BVOC emissions, and a chemical-transport model, shows that the adjusted parameterization provides a better agreement between the modelled and observed HCHO temporal variability at local and regional scales in 2011–2012, even if it worsens the model agreement in a global, long-term evaluation. We discuss the limitations of the current parameterization, a function of highly uncertain soil properties such as porosity.