The lack of affordable, available pediatric drug formulations presents serious global health challenges. This article argues that successful pharmacotherapy for children demands an interdisciplinary approach. There is a need to develop new medicines to address acute and chronic illnesses of children, but also to produce formulations of essential medicines to optimize stability, bioavailability, palatability, cost, accurate dosing and adherence. This, in turn, requires an understanding of the social ecologies in which treatment occurs. Understanding health worker, caregiver and patient practices, limitations, and expectations with regard to medicines is crucial to guiding effective drug development and administration. Using literature on pediatric tuberculosis as a reference, this review highlights sociocultural, pharmacological, and structural barriers that impede the delivery of medicines to children. It serves as a basis for the development of an intensive survey of patient, caregiver, and health care worker understandings of, and preferences for, pediatric formulations in three East African countries.