The mineralocortoid receptor (MR) regulates salt homeostasis in the kidneys and plays a range of other roles in the heart, vasculature, brain and adipose tissue. It interacts with both mineralocorticoids and glucocorticoids to mediate transcription of target genes. The ability of the MR to exert tissue- and ligand-specific effects relies on its interactions with a range of binding partners, including the chaperone proteins, coregulators, other transcription factors, DNA and modifying proteins. Interactions within the domains of the MR also modulate the overall transcriptional complex. This review will discuss the current understanding of interactions involving the MR and highlight their relevance to ligand- or tissue-specificity as well as their suitability as therapeutic targets.