Contemporary dentistry emphasizes the importance of preserving natural teeth whenever possible. Implementation of principles of evidence-based dentistry in endodontics enables the practitioner to provide the patient with the best available treatment in each clinical scenario. Advances in modern endodontic techniques and technologies have enhanced the ability to prevent, detect, and manage complications such as vertical root fractures, perforations, and root resorption. With proper case selection, teeth that were traditionally planned for extraction can be successfully treated through either nonsurgical or surgical endodontic approaches, achieving high success rates. This chapter aims to explore the endodontic perspective in clinical decision-making concerning the management and preservation of natural teeth. It addresses key topics, including endodontic case selection, treatment planning, long-term prognosis, innovative technologies and treatment modalities, and decision-making considerations for diagnosing and managing endodontic complications.