Neonatal seizures (NS) are the most frequent sign of neurological dysfunction in newborn infants. With increased survival of preterm neonates, the current clinical focus has shifted from preventing death to improving long-term neurological outcome. In the context of acute symptomatic NS, the main negative prognostic factors include etiology, and severity of brain injury, but also prolonged seizures and especially status epilepticus. However, the reasons for the detrimental contribution of seizures to outcome are still unclear, and evidence has been collected both in favor of seizures being an epiphenomenon of brain injury and of independently contributing to further damage. In this narrative focused review, we will discuss both hypotheses, with special emphasis on data relating to preterm infants. We will also identify present controversies and possible future lines of research.