The definition of “symptomatic” primary hyperparathyroidism (PHPT) has evolved since the disease was first described in the early twentieth century. In modernity, patients rarely present with classically symptomatic disease, and clinicians therefore have gradually expanded their views of what constitutes symptomatic PHPT to more appropriately capture all signs and markers of PHPT. This chapter explores the classic and modern clinical presentations of PHPT and the current indications for parathyroidectomy. Additionally, the effects of parathyroidectomy on target organ systems are reviewed as a means to define a broader view of what could be considered “symptomatic” PHPT.