With advancements in neonatal care, the survival rates of preterm infants have increased, leading to a higher incidence of comorbidities and need for surgical interventions. Neonatologists, pediatric anesthesiologists, and pediatric surgeons are thus increasingly confronted with the decision of whether to perform surgical procedures on critically ill neonates and preterm infants in the operating room (OR) or the NICU. Although certain bedside procedures have been commonly described in the literature, a paucity of research exists regarding ideal patient selection and anesthetic management. In this review, we will examine the decision-making process for providing anesthetic care in the OR versus the NICU as well as investigate appropriate sedation agents for procedures occurring in the NICU. Ultimately, the location of the surgery should be determined by the circumstances of each patient and involve collaboration of the entire perioperative team.