Isoprene is the most abundant non-methane volatile organic compound in Earth's atmosphere. It is emitted naturally by plants as a byproduct of photosynthesis, primarily in tropical regions. Isoprene has significant and complex impacts on atmospheric chemistry and air quality. For example, isoprene is a precursor to ozone and CO pollution in the lower troposphere. It is therefore essential that isoprene emissions can be accurately estimated. One of the most popular ways of estimating isoprene emissions is to use the MEGAN 2.1 emissions model. However, there are major discrepancies between these MEGAN 2.1 emissions estimates and those derived from observational data. In this talk, I will address these discrepancies by exploring the sensitivity of MEGAN 2.1 emissions estimates to different meteorological driving variables. I will show that the model's sensitivity to changes in surface temperature and leaf area index (i.e., the amount of vegetated land) varies widely across space and time. These variations negatively affect the model's ability to accurately reproduce the observed seasonal cycle of isoprene emissions in many regions.