Antimicrobial resistance and healthcare associated infections are major worldwide Public Health and Patient Safety challenges. Inappropriate antibiotic prescription is the major drive for antibiotic resistance and is present in 30 to 50% of all antibiotic prescriptions. However, adherence to guidelines and to computerized decision support systems is still poor, reflecting the complexity of the prescription process. Antimicrobial stewardship programs have been implemented aiming optimization of prescriptions. Assessment of individual prescriptions appropriateness is a major task and a pillar of these programs. Adoption of universal definitions of appropriateness and assessments, based on quality indicators, metrics and algorithms, is needed in order to improve classifications of individual prescriptions and its determinants, where new eHealth tools and ultimately artificial intelligence will be major allies. This text highlights the importance of evaluation of individual prescriptions as the major way to understand the determinants of (in)appropriate antibiotic prescription and the need for future developments. It mainly results from a comprehensive review of papers published since 2010, related to antimicrobial resistance, the prescription process, antimicrobial stewardship, as well the appropriateness of antibiotic prescription and its evaluation. The road is ahead!.