Despite being among the most ancient medications in a historic perspective, diuretics also hold the merit of representing an evergreen challenge for research and related drugs development. In this overview, we recapitulate the origin and evolution of diuretics, their mechanisms of action and their clinical applications. The physiologic basis of their functioning, as well as therapeutic and collateral desirable and adverse effects related to their use, will be discussed, with particular reference to their metabolic effects and connected acid/base changes. Current research developments will be also mentioned. A separate section is dedicated to aquaretics, to summarize their functioning, actions, clinical uses and limitations.
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