The recent development of highly multiplexed methods for imaging tissues from patients and mouse models promises to fundamentally advance research in tissue biology and disease. These new technologies enable the study of cell states, cell-cell interactions, and tissue architecture in normal and disease conditions. A common application of tissue imaging in oncology is identifying and enumerating immune cell types and mapping their locations relative to tumor and stromal cells. Such spatially-resolved data is pertinent to understanding the mechanisms of action of immunotherapies. These tools however can be applied to investigate a wide range of topics including stress responses and cell cycle regulation. The ability to extract high-dimensional information from single cells within their native context provides a distinct opportunity to understand complex cell biologic principles underlying disease pathogenesis.