After a brief historical recall, this review states the needs for an accurate diagnosis of the neonatal respiratory distress syndrome (RDS). The clinical features consist of disturbances of respiratory rate, grunting, intercostal retractions, and cyanosis, but early mechanical ventilation tends to suppress most of them. Laboratory findings include hypoxemia, hypercapnia, and mixed acidosis. Positive radiological diagnosis remains an important criterion but early ventilation with positive end-expiratory pressure has made grading obsolete. The biochemical diagnosis addresses the basic lung surfactant deficiency, by determination of the lecithin/sphingomyelin ratio and phosphatidylglycerol ("modified lung profile") in lung effluents at birth. If clinical and radiological diagnosis remains adequate for daily practice and epidemiological studies, biochemical diagnosis should be mandatory for therapeutic trials. However, the problem of atypical RDS in very low birth weight infants has not been totally solved. RDS has now been known for more than 80 years; yet its diagnosis is still a matter of controversy.