The last decade has seen herpes simplex virus (HSV)-induced stromal keratitis (SK) research shift from being a topic only of interest to vision researchers to one that fascinates the general field of inflammatory disease. Studies on experimental mouse lesions have uncovered several fundamental processes that explain lesion development. In this model, the chronic immuno-inflammatory lesions are mainly orchestrated by CD4+ T cells, but multiple early events occur that set the stage for the subsequent pathology. These include virus replication, the production of key cytokines and chemokines, neovascularization of the avascular cornea and the influx of certain inflammatory cell types. Many of these early events are subject to modulation, providing an approach to controlling this important cause of human blindness. We also comment on events ongoing during chronic SK, debating whether or not these represent virus-induced or autoimmune lesions.