Background: Less invasive surfactant administration (LISA) has become the preferred method of surfactant administration for spontaneously breathing babies on continuous positive airway pressure (CPAP). Summary: The development of LISA followed the need to combine CPAP and surfactant replacement as mainstay treatment options for respiratory distress syndrome, thereby avoided exposure to positive pressure ventilation. Key Messages: This review summarises the current knowns and unknowns of LISA including the physiological concept, its relevance for short-term and long-term outcomes and the challenges for practical implementation of LISA as part of a less invasive respiratory care bundle. Further, we provide an update of the evidence on alternatives to LISA, for example, nebulised surfactant administration, pharyngeal deposition of surfactant and delivery via supraglottic airway.