Presentation of corneal antigens for induction of adaptive immune responses is mediated by corneal antigen-presenting cells (APC), including those that infiltrate the cornea in response to inflammatory stimuli and, to a lesser extent, those that reside in the cornea and up-regulate activation markers in response to inflammation. Significant progress has been made in the last decade in dissecting the molecular mechanisms that mediate APC infiltration into the cornea. However, it has recently been determined that exit of APC out of the cornea is critical for induction of T cells that normally reside outside of the cornea in lymphoid reservoirs. Much less is understood about the molecular regulation of APC egress from the cornea, but our laboratory has recently discovered that APC access to afferent lymphatics and draining lymph nodes requires signaling mediated by VEGFR-3. We describe herein the functional implication of APC trafficking and the prospects for novel immunomodulatory strategies based on regulating APC migration.