Dose-finding studies of influenza antiviral drugs are challenging because it is difficult to enroll subjects in pediatric interventional studies and also because of the lack of concentration (or toxicity)–response relationships, the short duration of antiviral therapy, and the continually developing metabolic profiles of infants and young children. The evaluation of influenza antiviral agents in premature infants adds even more complexity. Recent advances in exposure-targeted study designs and modeling and simulations have aided in addressing some of these challenges.