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The clinical practice of endodontics tends to focus more on the actual mechanical aspect of treatment. This aspect relates to the types of rotary files used, canal medicament, and obturation material and techniques. Although the mechanical aspect of endodontic treatment is important, it is paramount that a dentist incorporates proper endodontic diagnostic and treatment planning skills before performing clinical endodontic treatment. This article will review endodontic diagnosis and treatment planning involving various medical or dental conditions that can have a direct or indirect effect on the actual treatment as well as the long-term prognosis after endodontic treatment is completed.