A 59-year-old woman underwent plate fixation of her 2-part anatomic neck proximal humerus fracture through an open anterolateral approach. The fixation subsequently failed, and the operation resulted in a dense axillary nerve palsy. Six weeks after her initial procedure, she was returned to the operating room. Exploration of the nerve revealed that it was compressed beneath the plate and irreparably damaged. Sural nerve cable grafting was required in an attempt to salvage deltoid function. The recent introduction of proximal humeral locking plates provides an opportunity for surgeons to reevaluate their methods of managing proximal humerus fractures. Indications for operative fixation have broadened, and a renewed interest in the anterolateral surgical approach has been reported. This case is the first description of an axillary nerve injury occurring in association with the open anterolateral approach when used for the treatment of a proximal humerus fracture and serves as a reminder that surgeons considering the use of a lateral approach must have a thorough understanding of axillary nerve anatomy. An additional review of the case provides a forum for discussion of the anterolateral approach to the proximal humerus and an opportunity to highlight the methods that can be used to optimize fixation when locked plates are employed. It must be emphasized that our enthusiasm for advances in technique and technology should not distract from basic surgical principles when treating these fractures.