The RASSF proteins are a family of polypeptides, each containing a conserved Ras association domain, suggesting that these scaffold proteins may be effectors of activated Ras or Ras-related small GTPases. RASSF proteins are characterized by their ability to inhibit cell growth and proliferation while promoting cell death. RASSF1 isoform A is an established tumor suppressor and is frequently silenced in a variety of tumors and human cancer cell lines. However, our understanding of its function in terminally differentiated cell types, such as cardiac myocytes, is relatively nascent. Herein, we review the role of RASSF1A in cardiac physiology and disease and highlight signaling pathways that mediate its function.