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Precision Medicine is an approach to disease treatment and prevention taking into account individual genetic, environmental, therapeutic and lifestyle variability for each person. This holistic approach to therapeutics is intended to enhance drug efficacy and safety not only across healthcare systems but for individual patients. While weight and to some extent gestational age have been considered in determining drug dosing in children, historically other factors including genetic variability have not been factored into therapeutic decision making. As our knowledge of the role of ontogeny and genetics in determining drug efficacy and safety has expanded, these insights have provided new opportunities to apply principles of Precision Medicine to the care of infants, children and youth. These opportunities are most likely to be achieved first in select sub-groups of children. While there are many challenges to the successful implementation of Precision Medicine in children including the need to ensure that Precision Medicine enhances rather than reduces equity in children’s health care rather, there are many more opportunities. Research, advocacy, planning and teamwork are required to move Precision Medicine forward in children in pursuit of the common goal of safe and effective drug therapy.