Anti-inflammatory agents, antipyretics, and antibiotics are commonly used to manage fever and pain associated with infectious diseases in both adults and children. Despite their effectiveness, inappropriate and unnecessary prescriptions remain widespread, leading to adverse patient outcomes and, in the case of antibiotics, contributing to antimicrobial resistance. Addressing these issues requires effective stewardship programs focused on educating healthcare professionals and the public on evidence-based guidelines for optimal prescribing practices. This paper explores the five "A"s fundamental to infection management in pediatric and adult patients: appropriateness, abuse, antipyretics, anti-inflammatory agents, and antibiotics. Through a comprehensive literature review, expert perspectives, and clinical guidelines, the study evaluates the roles of anti-inflammatory agents (e.g., ibuprofen), antipyretics (e.g., paracetamol), and antibiotics in clinical practice, highlighting best practices for their use. Experts’ suggestion emphasize that antipyretics should only be administered when fever is accompanied by significant discomfort or pain, as fever itself plays a role in the immune response. Paracetamol is generally preferred as a first-line antipyretic due to its favorable safety profile, while ibuprofen should be used with caution, particularly during respiratory infections, varicella, and severe bacterial infections, due to its potential to exacerbate complications. Special consideration is also required for patients with renal or gastrointestinal comorbidities to prevent toxicity. Regarding antibiotics, prescription should be limited to clear evidence of bacterial infection to avoid unnecessary patient exposure and the development of antimicrobial resistance. Stewardship programs underscore the importance of selecting the right agent, optimizing dosing, and introducing shorter treatment regimens where supported by evidence, to improve therapeutic outcomes while minimizing resistance risks. Ultimately, this paper provides practical, evidence-based recommendations to support rational prescribing of antipyretics, anti-inflammatory drugs, and antibiotics, aiming to optimize patient outcomes, prevent unnecessary toxicity, and contribute to global efforts against antimicrobial resistance.