Mast cells (MCs) are heterogeneous tissue-resident effector cells that are thought to play central roles in allergic inflammatory disease, yet the degree of heterogeneity and nature of these roles has remained elusive. In recent years, advances in tissue culture systems, preclinical mouse models, and the continued spread of single-cell RNA sequencing have greatly advanced our understanding of MC phenotypes in health and disease. These approaches have identified novel interactions of MC subsets with immune cells, neurons, and tissue structural cells, changing our understanding of how MCs both drive and help resolve tissue inflammation, reshape tissue microenvironments, and influence host behavior. This review addresses key studies from 2022 to 2024 that have advanced our understanding of MC biology in mice and humans.