At sites impacted by volatile organic compounds (VOCs), vapor intrusion (VI) is the pathway with the greatest potential to result in actual human exposure. Since sites with VI were first widely publicized in late 1990s, the scientific understanding of VI has evolved considerably. The VI conceptual model has been extended beyond relatively simple scenarios to include nuances, such as biological and hydrogeological factors that may limit the potential for VI and alternative pathways, such as preferential pathways and direct building contact/infiltration that may enhance VI in some cases. Regulatory guidance documents typically recommend initial concentration-or distance-based screening to evaluate whether VI may be a concern, followed by a multiple-lines-of-evidence (MLE) investigation approach for sites that do not screen out. These recommendations for detailed evaluation of VI currently focus on monitoring of VOC concentrations in groundwater, soil gas, and indoor air and can be supplemented by other lines of evidence. In this Critical Review, we summarize key elements important to VI site characterization, provide the status and current understanding, and highlight data interpretation challenges, as well as innovative tools developed to help overcome the challenges. Although there have been significant advances in the understanding of VI in the past 20 years, limitations and knowledge gaps in screening, investigation methods, and modeling approaches still exist. Potential areas for further research include improved initial screening methods that account for the site-specific role of barriers, improved understanding of preferential pathways, and systematic study of buildings and infrastructure other than single-family residences.