Analgesic dosing regimens should take into account the severity and type of pain, the therapeutic window of the drug, and also the age or developmental state of the child. Translation of these concepts to safe and effective pharmacological management of pain in neonates, infants, and children necessitates a thorough understanding of the principles of clinical pharmacology of analgesics in children. Growth, weight or size, and maturation or age evolve in children and profoundly affect the pharmacokinetics (concentration–time profile, absorption, distribution, metabolism, and excretion) and pharmacodynamics (concentration–effect profile, objective assessment) of drugs, and this is also the case for analgesics. This will result in extensive variability in dosing and effects throughout childhood, and this variability is most prominent in infancy. In addition to maturational changes, there are also nonmaturational aspects (preterm neonates and critical illness, obesity, pharmacogenetics) that should be considered to further improve dosing in every individual child.