In the last decade, GER pharmacological treatment has increasingly widespread in NICUs. The provision of anti-histamine2 (H2) blockers and proton pump inhibitors (PPI) in the preterm population, however, might lead to such adverse effects as an increased incidence of necrotizing enterocolitis and infections. Hence, to avoid a useless and potentially harmful pharmacological overtreatment, a step-wise approach, firstly promoting conservative strategies, is currently considered the most advisable choice for GER management in symptomatic preterm infants.