Thirty years ago, Dr Harry Shirkey recognized the serious dilemma of pediatric drug labeling, called therapeutic orphan, to capture its concept, and described remedial measures to minimize the dilemma. This review offers a brief exposition of the therapeutic orphan's arduous journey toward the goal of labeling of all drugs used for children. Aside from legal and US Food and Drug Administration (FDA) policy requirements to secure new drug application approval to market a drug, some may question reasons for a pediatric drug label, especially if a label exists for adult use and pediatric use information is distributed in literature reports. Major pragmatic reasons for a pediatric label are presented in Table 1. A label testifies to carefully reviewed clinical trial data that offer substantial evidence to support pediatric indications for which the drug has approved use. Perhaps of unappreciated importance is availability of information on the label. Time-consuming literature review and analysis often are not necessary when a pediatric label exists. Label information is compiled for the pediatric drug formulation, and it is this formulation that is approved. Literature reports often contain one or more formulations prepared by the investigator, and good manufacturing procedures or bioavailability estimates may be less than desired. A formulation on the label frequently has been evaluated for characteristics acceptable to children and hence compliance is strengthened. The drug, having met pediatric labeling requirements, is available for children and obviates the awkward double standard—one for adults (label necessary for marketing) and one for children (pediatric label not necessary for marketing or use). To the lay public, this pediatric labeling allows third-party reimbursement of drug costs otherwise denied. This relieves young parents of a truly indefensible economic burden, which in some cases has denied drug treatment to children. Add to this the refusal of some malpractice … Address correspondence to John T. Wilson, MD, Section on Clinical Pharmacology, Department of Pediatrics, Louisiana State University Medical Center, Shreveport, LA 71130.