Survival of extremely preterm and critically ill neonates has improved significantly over the last few decades following advances in neonatal intensive care. These include antenatal glucocorticoids, surfactant, continuous positive airway pressure support, advanced gentle modes of ventilation and inhaled nitric oxide. Probiotic supplementation is a recent significant milestone in the history of neonatal intensive care. Very few, if any, interventions match the ability of probiotics to significantly reduce the risk of death and definite necrotising enterocolitis while facilitating enteral feeds in high‐risk preterm neonates. Probiotics also have a potential to benefit neonates with surgical conditions with significant gastrointestinal morbidity. Current evidence for the benefits of probiotic supplementation for neonates in an intensive care unit is reviewed. The mechanisms for the benefits of probiotics in this population are discussed, and guidelines for clinicians are provided in the context of the regulatory framework in Australia.