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Significance Peripheral nerve injury is a major neurological disorder that can cause multiple motor and sensory disturbances. In this study we found that VEGF-B can be used as a previously unidentified therapeutic for treating peripheral nerve injury. We demonstrated that VEGF-B stimulated nerve regeneration and enhanced the recovery of both tissue sensation and the ability of nerves to enhance healing of innervated tissue. The physiologic relevance of VEGF-B is demonstrated by our findings showing that mice lacking VEGF-B have impaired nerve regeneration and that nerve injury resulted in increased endogenous expression of VEGF-B. We discover that VEGF-B induces strong elongation and branching of neurons and requires specific transmembrane receptors as well as activation of a complex intracellular signaling. VEGF-B primarily provides neuroprotection and improves survival in CNS-derived neurons. However, its actions on the peripheral nervous system have been less characterized. We examined whether VEGF-B mediates peripheral nerve repair. We found that VEGF-B induced extensive neurite growth and branching in trigeminal ganglia neurons in a manner that required selective activation of transmembrane receptors and was distinct from VEGF-A–induced neuronal growth. VEGF-B–induced neurite elongation required PI3K and Notch signaling. In vivo, VEGF-B is required for normal nerve regeneration: mice lacking VEGF-B showed impaired nerve repair with concomitant impaired trophic function. VEGF-B treatment increased nerve regeneration, sensation recovery, and trophic functions of injured corneal peripheral nerves in VEGF-B–deficient and wild-type animals, without affecting uninjured nerves. These selective effects of VEGF-B on injured nerves and its lack of angiogenic activity makes VEGF-B a suitable therapeutic target to treat nerve injury.