Pain is a common symptom in endodontic conditions, but differential diagnostic procedures are often needed to exclude other pain origins. General dentists and endodontists thus need to be aware of alternative painful orofacial conditions, and be able to identify them. The new International Classification of Orofacial Pain (ICOP, 2020) is the first comprehensive classification that uniquely deals with orofacial pain. The ICOP is a hierarchical classification, modelled on the International Classification of Headache Disorders (ICHD-3) and covers pain in dentoalveolar and anatomically related tissues, muscle pain, temporomandibular joint (TMJ) pain, neuropathic pain affecting cranial nerves, pain resembling primary headaches, and idiopathic pain in the orofacial region. A description of each condition is given, and structured diagnostic criteria for each condition are proposed based on research data when available. This narrative review aims to (i) give an overview and brief explanation of the ICOP system, (ii) describe and give examples of how it can be of use to general dentists and endodontists with special attention to differential diagnosis of tooth pain, and (iii) highlight how endodontic research can contribute to validation and improvement of the classification. A comparison to other classification and diagnostic systems is also included.