The immune system is a complex, dynamic, and plastic ecosystem composed of multiple cell types that constantly sense and interact with their local microenvironment to protect from infection and maintain homeostasis. For over a century, great efforts and ingenuity have been applied to the characterization of immune cells and their microenvironments, but traditional marker-based and bulk technologies left key questions unanswered. In the past decade, the advent of single-cell genomic approaches has revolutionized our knowledge of the cellular and molecular makeup of the immune system. In this perspective, we outline the past, present, and future applications of single-cell genomics in immunology and discuss how the integration of multiomics at the single-cell level will pave the way for future advances in immunology research and clinical translation.