Despite recent advances in acute stroke care, clinical armamentarium against stroke remains limited. Furthermore, highly effective approaches to stroke treatment, such as systemic reperfusion and mechanical thrombectomy, cannot be performed in the majority of patients. Neuroprotective strategies, i.e. prevention of irreversible cell damage due to the ischemia, may improve stroke outcomes. However, only few pharmacological agents demonstrated clinical efficacy. Citicoline is an endogenous mononucleotide with neuroprotective effect and established clinical safety and tolerability, which effectiveness in acute stroke was studied in several large, well-controlled trials. Recent meta-analysis confirmed benefit of citicoline treatment in terms of increase of chance for better recovery of functional independence compared to placebo. Maximal effect of citicoline is seen when it is administered as soon as possible after stroke onset in patients who are not eligible for reperfusion therapy.