Urine drug testing is critical in managing the opioid crisis by providing insights into patient compliance and potential abuse. This review emphasizes the adoption of strategic approaches to improve test ordering and enhance the accuracy of interpretations. Risk assessment, pathologist oversight, and the application of a reflex algorithm can streamline laboratory workflows and support accurate interpretations, especially when navigating limitations from different testing methodology. Informatics tools can further optimize data analysis and testing workflows by increasing efficiency and integrating relevant clinical information. Together, these approaches lead to more effective urine drug testing, and ultimately improved patient care.