The vadose zone can be characterized as a complex subsurface system in which intricate physical and biogeochemical processes occur in response to a variety of natural forces and human activities. This makes it difficult to describe, understand, and predict the behavior of this specific subsurface system. The TOUGH nonisothermal multiphase flow simulators are well suited to perform advanced vadose zone studies. The conceptual models underlying the TOUGH simulators are capable of representing features specific to the vadose zone, and of addressing a variety of coupled phenomena. Moreover, the simulators are integrated into software tools that enable advanced data analysis, optimization, and system-level modeling. We discuss fundamental and computational challenges in simulating vadose zone processes, review recent advances in modeling such systems, and demonstrate some capabilities of the TOUGH suite of codes using illustrative examples.