This study aimed to review the considerations for choosing a suitable sealer according to various endodontic scenarios. An electronic search of PubMed, Scopus, and the Web of Science was undertaken for the keywords of ‘sealer choosing’, ‘appropriate sealer’, ‘suitable sealer’, ‘sealer for clinical scenario’, and ‘sealer for clinical situations’. However, the literature review revealed a lack of studies with practical clinical recommendations regarding the choice of appropriate endodontic root canal sealers for particular clinical situations of root canal treatment. Therefore, a narrative review was undertaken under the basis of the characteristics of an epoxy resin-based sealer (ERS) versus a calcium silicate-based sealer (CSS). Based on the evidence found through the review, the choice of an appropriate sealer in a variety of clinical scenarios was proposed. An ERS is recommended for one-visit non-vital cases, teeth with periodontal involvement, cracked teeth, and internal root resorption without root perforation. A CSS is recommended for vital or non-vital cases in multiple visits, teeth with internal root resorption with perforation or internal approach for external cervical resorption, teeth with open apices, and teeth with iatrogenic aberrations.