Seizures are the most acute evident manifestation of central nervous system dysfunction in neonates. The incidence is higher in very low weight neonates, about 58/100 live births, as opposed to full-term infants, estimated about 3.5/100 live births. Neonatal seizures represent the clinical manifestation of a non-specific disorder of cortical cerebral dysfunction, which could lead to permanent brain injury. The etiology is multifactorial and requires a judicious assessment of each clinical scenario. The diagnosis and its management are further complicated as most neonatal seizures may have very subtle or no clinical changes and the diagnosis may be just based on EEG findings, so-called subclinical. The treatment is dependent on the etiology, but early and opportune intervention can prevent further brain damage and improve prognosis. Although early identification and treatment are essential, the diagnosis of neonatal seizures can be further complicated by the clinical presentations, possible etiologies, and treatments. Nevertheless, research studies and clinical evidence have shown that early treatment with anti-seizure medications can change the outcome.