This editorial examines the ongoing challenges associated with developing and implementing clinical practice guidelines (CPGs), sparked by Ng et al.'s analysis of pre-participation physical evaluations (PPE) for youth athletes. The authors reveal that only a third of the PPE evaluation they reviewed documented all essential patient history elements. They suggest that the limited efficacy of PPEs in predicting serious cardiac events may lead practitioners to deprioritize comprehensive history-taking, and point to the stronger evidence for electrocardiograms (ECG) as a more effective diagnostic tool. Practitioners should reflect more broadly on the inherent tension between CPG standardization and the need for clinical flexibility. While standardized guidelines are crucial for consistent, high-quality care in acute and chronic settings, social determinants of health (SDH) can affect patient adherence and outcomes, necessitating tailored approaches, which can account for the disparities in CPG application across different populations and healthcare environments. Complex guidelines can be overwhelming, particularly in under-resourced settings, where they may be impractical or difficult to follow. For these areas, CPGs should account for local infrastructure and healthcare capabilities, potentially substituting advanced diagnostics with enhanced clinical skills. There are additional concerns about CPG development processes, including the variability in expert opinions, the influence of industry funding, and conflicts of interest that may erode trust and compliance. While industry contributions can enhance guideline robustness, transparency and accountability are vital to maintaining the integrity of CPGs. In conclusion, we call for a pragmatic approach to CPG development that balances scientific rigor with adaptability to diverse clinical and resource-limited settings. Addressing these challenges is essential for fostering equitable and effective patient care and enhancing the trustworthiness of CPGs in the global healthcare landscape.