| Summary: | The nucleus of a cardiomyocyte has been increasingly recognized as a morphologically distinct and partially independent calcium (Ca<sup>2+</sup>) signaling microdomain, with its own Ca<sup>2+</sup>-regulatory mechanisms and important effects on cardiac gene expression. In this review, we (1) provide a comprehensive overview of the current state of research on the dynamics and regulation of nuclear Ca<sup>2+</sup> signaling in cardiomyocytes, (2) address the role of nuclear Ca<sup>2+</sup> in the development and progression of cardiac pathologies, such as heart failure and atrial fibrillation, and (3) discuss novel aspects of experimental methods to investigate nuclear Ca<sup>2+</sup> handling and its downstream effects in the heart. Finally, we highlight current challenges and limitations and recommend future directions for addressing key open questions.
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