Newborns suffering from perinatal arterial ischemic stroke (PAIS) are at risk of neurodevelopmental problems. Current treatment options for PAIS are limited and mainly focus on supportive care, as presentation of PAIS is beyond the time window of current treatment strategies. Therefore, recent focus has shifted to interventions that stimulate regeneration of damaged brain tissue. From animal models, it is known that the brain increases its neurogenic capability after ischemic injury, by promoting neural cell proliferation and differentiation. However, neurogenesis is not maintained at the long term, which consequently impedes full repair leading to adverse consequences later in life. Boosting neuroregeneration of the newborn brain using treatment with neurotrophic factors and/or mesenchymal stem cells (MSCs) may be promising novel therapeutic strategies to improve neurological prospects and quality of life of infants with PAIS. This review focuses on effectiveness of neurotrophic growth factors, including erythropoietin, brain-derived neurotrophic factor, vascular endothelial growth factor, glial-derived neurotrophic factor, and MSC therapy, in both experimental neonatal stroke studies and first clinical trials for neonatal ischemic brain injury.