Most proximal humeral fractures occur in elderly patients, and can be treated non-operatively with good functional outcomes. Percutaneous, intramedullary, and locked-plate fixation can be successful fixation strategies for proximal humeral fractures, with the correct indications and careful patient selection, based on the anatomy and biomechanics of the injury. Each method has its advantages and disadvantages. A variety of underlying factors have to be considered, related to the patient (e.g., comorbidity, functional demand), the fracture (e.g., osteoporosis), and the surgeon (e.g., experience). Low local bone mineral density, humeral head ischaemia, residual varus displacement, insufficient restoration of the medial column, and non-anatomic reduction promote failure of fixation and impair functional outcome. Regardless of the technique selected, meticulous surgical technique and anatomic reduction, MIPO and respect of soft tissues are essential.