Neonatal hypoxic-ischemic (HI) injury still remains an important issue as it is a frequent cause of neonatal death and life-long neurobehavioral and cognitive dysfunction. In spite of the decades of research which led us to a better knowledge of the pathological mechanism of hypoxic-ischemic brain injury, the clinical use of potential neuroprotective drugs (including, among others, excitatory amino acids antagonists, free radical inhibitors and scavengers, growth factors, xenon, cannabinoids, anti-inflammatory and anti-apoptotic agents) became avoided owing to insufficiency and /or treatment-induced undesirable side effects. The only available effective treatment, hypothermia, neither provides complete brain protection nor stimulates the repair necessary for neurodevelopmental outcome. This fact brings about increased interest in alternative methods of therapy, such as regenerative medicine using stem cells. Growing number of in vivo preclinical studies revealed that mesenchymal stem cells as well as human cord blood cells may improve functional outcome after HI insult and may represent a new beneficial treatment modality for infants developing hypoxic-ischemic encephalopathy. In this review we briefly highlight the present and potential forthcoming therapeutic treatments aimed at attenuation of the detrimental effects of neonatal hypoxia-ischemia.