A thorough anatomical knowledge is very essential for clinical practice and any surgical procedure. Unfortunately anatomical variations can lead to hazards in medical and dental diagnosis and treatment. Such knowledge is very essential even in effective local anesthesia which is an essential part of treatment in patients with many oral disorders. Therefore a normal anatomy and its possible variations are utmost important aspects also in dentistry. One of the structures that dentists very often deal with is the mandibular nerve which therefore needs a thorough review. However, there are not many consolidated literature reviews available regarding its variations and clinical applications. Keeping this in mind, in this article, the authors have brought together available literature on various aspects of mandibular nerve. The final review will be of benefit to clinicians (Fig. 2, Ref. 63).