Opioid-free anesthesia (OFA) represents an innovative approach that prioritizes patient safety, reduces the risks associated with opioid use, and seeks to enhance recovery. Few descriptions regarding the practical and implementation aspects exist. This review serves as a practical guide on OFA teaching and application. We briefly discuss the historical use of opioids in anesthesia, side effects and their consequences. We discuss pedagogical avenues and challenges, as well as implementation of OFA in less experienced settings. Opioid use in anesthesia originally coexisted with OFA. During the last decades, the advent of multimodal analgesia has resulted in decreased opioid dosages both before and after surgery. Recently, OFA increased in popularity, supported by meta-analyses, due to reduced nausea and vomiting, with a potential, even if limited, impact on pain. OFA, as part of rational prescribing, may contribute to a more patient-centered approach. Different strategies for OFA implementation coexist. Educational aspects, leadership, guidelines, local guidance, and training are all important. We propose a framework for OFA implementation with concrete options, including patient preparation, choice of OFA pharmacological agents (according to type of surgery and patient), and postoperative care. Whilst opioids still have an important place in pain management, they have brought harms that we cannot ignore. Evidence for using opioid-sparing and OFA techniques continues to emerge and there is a need to personalize more approaches. In this review, we provide evidence-based, relatively simple methods that can be used in implementing and delivering OFA.