The majority of neonatal seizures are of acute symptomatic origin, and their occurrence is associated with higher mortality and morbidity compared with the general population, even if there is conflicting evidence of a detrimental effect per se. Etiology is considered the main determinant of outcome, but other factors, including gestational age, brain damage severity, neonatal neurological examination, and electroencephalographically (EEG) interictal and ictal characteristics are also related to neurodevelopmental outcome or death. Therefore, accuracy in early prognostication since the neonatal period can be improved by conveniently integrating different clinical and instrumental findings. The aim of this review is first to review the outcome of newborns with seizures (mortality, epilepsy, cerebral palsy, and intellectual disability), second to review the risk factors for adverse outcome after seizures in the newborn period, considering clinical, EEG/amplitude-integrated EEG, and neuroimaging findings associated with adverse outcome and lack of response to treatment, and finally to review published scoring systems for predicting neurologic outcome after neonatal seizures. The topic of this review has been presented at the “Progress in epileptic disorders workshop. Seizures of onset in the first two years of life,” Rome November 14 to 17, 2013, in a conference as well as a manuscript format. The latter is due to be published as a corresponding book chapter, in a more extended and complete form than in this review.