Metabolic acidosis is common in preterm and term newborn infants and may be attributed to a variety of etiologies, potentially requiring base therapy such as acetate or bicarbonate. However, concerns exist regarding potential harm of sodium bicarbonate due to intracellular acidosis, fluctuations in cerebral blood flow, and osmolar load with rapid infusions, with no improvement in survival when used during resuscitation. Alternative approaches to correct metabolic acidosis include the addition of acetate in parenteral nutrition, intravenous lactated Ringer's (LR) solution, and use of oral citrate. Current guidelines focus on addressing the underlying cause of acidosis, reserving the use of sodium bicarbonate (NaHCO) for severe cases requiring acute correction, LR instead of saline for volume boluses and using acetate or citrate for slow correction to stabilize acid-base status. Further research is necessary to better understand the efficacy and safety of acetate, NaHCO, and other base sources in treating metabolic acidosis in neonates.