The relationship between suboptimal use of antimicrobials and antimicrobial resistance has become increasingly clear. Despite significant international effort aimed at reducing inappropriate antimicrobial prescribing in hospitals, antimicrobial resistance remains a major public health threat. Antimicrobial Stewardship Programs (ASPs) comprise a series of measures aimed at optimizing the use of antimicrobials, while improving the quality of patient care and promoting cost-effectiveness. This discussion article aims to summarize some of the approaches that have been used in neonatal and pediatric ASPs, with a particular focus on the European healthcare setting. Current evidence demonstrates neonatal and pediatric ASPs to be safe, practical to implement, generally cost-effective and possibly associated with a reduction in antimicrobial resistance rates. This review identified that, despite the recognized need for additional evidence and information on implementation, published data on pediatric ASPs derives mainly from the United States, with very few published reports on formal ASPs in European children’s hospitals. Consequently, the optimal method of implementation remains unknown within a European setting. Future research needs to include novel study designs on how best to introduce ASPs, monitoring of clinically relevant outcomes and cost-effectiveness with improved measurement of the impact on antimicrobial resistance.