Indications for administration of surfactant to infants with established respiratory distress syndrome (RDS; rescue therapy) remains an area of continued investigation. Current recommendations vary from use in infants who are intubated and have an aAPO2 <0.22 to use in infants receiving >/=40% oxygen administered in a hood when the PaO2 is <80 TORR (aAPO2 approximately <0.36). This commentary is written in response to the article by Verder et al, in this issue of Pediatrics, who evaluated early versus late treatment of RDS in 60 preterm infants <30 weeks' gestation receiving nasal continuous positive airway pressure (CPAP). Early-treated infants (aAPO2, 0.22 to 0.35; mean, 0.26) had a lower incidence of mechanical ventilation or death (21%) than did late-treated infants (63%), who did not receive surfactant treatment until the aAPO2 was <0.22 (0.15 to 0.21; mean, 0.16). The authors conclude that although approximately half of infants <30 weeks' gestation with RDS can be treated with nasal CPAP alone, early treatment with surfactant when the aAPO2 is 0.22 to 0.36 reduced significantly the need for mechanical ventilation. Limitations of applicability of the study to widespread use include determination of PO2 values from transcutaneous measurements, which may vary from those obtained from arterial samples and affect significantly aAPO2 ratios. Likewise, use of nasal CPAP significantly affects oxygenation, and interpretation of results cannot be extrapolated to intubated infants or those receiving oxygen delivered under a hood. Nonetheless, the use of the aAPO2 ratio and early administration of surfactant are supported by this study.