Mesoscale convective systems (MCSs) account for a large fraction of mean and extreme precipitation in many regions around the world. In the U.S. east of the Rocky Mountains, MCSs are responsible for most of the slow-rising and hybrid floods because of their high intensity rainfall and large area coverage. Changes in thermodynamic environments and large-scale circulations with warming could influence the initiation and characteristics of MCSs, motivating the need to understand how MCSs and their hydrologic impacts may change in the future. MCSs are notoriously difficult to simulate, as even convection permitting simulations underestimate MCS number and precipitation in many regions. Using observations and a hierarchy of models and analysis tools, we study MCSs, their large-scale environments, their role in land-atmosphere interactions, and the mechanisms of their response to global warming and implications for hydrologic variability and change.