In the herpetic stromal keratitis (HSK), HSV DNA fragments and HSV-IgG immune complexes (HSV-IC) are present in most of the corneas long after infective virus has disappeared. These viral components are highly immunogenic and potentiate production of proinflammatory cytokines and chemokines via Toll-like receptors (TLRs) expressed on the corneal cells and macrophages. In addition angiogenic factors, such as vascular endothelium growth factor (VEGF) and the tissue damaging enzyme matrix metalloproteinase 9 (MMP-9) deeply involved in the pathogenesis of HSK, are also induced by corneal cells and macrophages through the recognition of these viral components. These processes elicited by residual viral DNA and HSV-IC are likely one of the sustained driving force in the development of HSK. Hence, strategies developed to alter these pathways should lead to new preventative and therapeutic measures.