The mineralocorticoid receptor (MR) has a direct role in cardiac physiology and disease and is a useful therapeutic target for patients with heart failure. However, significant side effects from mineralocorticoid receptor antagonist (MRA) treatment in up to 10% of patients has prompted efforts to identify new tissue specific mechanisms that may allow for selective MR therapies. Recent studies have identified the circadian clock as a novel, reciprocal interacting partner of the MR in the heart. While the closely related glucocorticoid receptor (GR) and its ligand, cortisol (corticosterone in rodents), are established regulators of the circadian clock, new data from this laboratory suggest that the MR can also regulate circadian clock gene expression and timing. Our recent data have revealed that MR signalling is modified by circadian transcription factors CLOCK and BMAL and thus by circadian time in vivo. Moreover, mRNA levels for the MR also follow a circadian pattern of expression. Taken together these data demonstrate a set of novel mechanisms whereby the always occupied MR may variations control of transcriptional activity. Moreover, defining the role of the MR and its ligands for the regulation of the molecular clock in the heart and other tissues has important implications for understanding dysregulation of these systems for cardiac disease progression, and for MR activation more broadly.