Primary aldosteronism is common and contributes to adverse cardiovascular, kidney, and metabolic outcomes. When instituted early and effectively, targeted therapies can mitigate these adverse outcomes. Surgical adrenalectomy is among the most effective treatments because it has the potential to cure, or attenuate the severity of, pathologic aldosterone excess, resulting in a host of biochemical and clinical changes that improve health outcomes. Herein, we review the role of surgical adrenalectomy in primary aldosteronism while emphasizing the physiologic ramifications of surgical intervention, and compare these to other targeted medical therapies for primary aldosteronism. We specifically review the role of curative adrenalectomy for unilateral primary aldosteronism, the role of non-curative adrenalectomy for bilateral primary aldosteronism, and how these interventions influence biochemical and clinical outcomes in relation to medical therapies for primary aldosteronism.