Aldosterone or glucocorticoid stimulation of the mineralocorticoid receptor (MR) is involved in numerous physiological responses, including ions and water homeostasis, blood pressure control and metabolism. The understanding of MR signaling regulation in the patho/physiological context took a new direction the last few years with a focus on the post-translational modifications of MR. Depending on its environment, cellular expression, activity or its binding partners, the MR is submitted to several post-translational modifications such as phosphorylation, ubiquitylation, sumoylation and acetylation that regulate its localization, activity and/or stability. A complex interplay between all these modifications allows a fine tuning of MR signaling depending on the physiological context. This review reports recent knowledge about post-translational modifications of MR and describes the enzymes and the molecular mechanisms involved.