Neurotrophic keratopathy is an ocular pathological condition that remains difficult to treat. The loss of trigeminal nerve function and corneal sensation that underlies this condition can lead to the development of various disorders of the cornea. Substance P, a sensory neurotransmitter produced by the trigeminal nerve, has been investigated for its effect on corneal epithelial wound healing. Substance P by itself has no direct effect on corneal epithelial migration, but it manifests a synergistic action with insulin-like growth factor-1 (IGF-1) in both epithelial migration in vitro and corneal wound healing in vivo. The minimal amino acid sequences of both substance P and IGF-1 that are required for such effects have been determined. With use of these minimal amino acid sequences, the potential adverse consequences of treatment with the full-length polypeptides may be avoided. The application of eye drops containing a substance P-derived peptide and IGF-1 has proved clinically effective for the treatment of patients with persistent epithelial defects of the cornea.