Despite almost a 70% decrease in the cardiovascular death rate over the past 50 years, heart disease remains the number 1 killer worldwide, claiming over 600,000 lives every year in the U.S. alone (23% of all-cause mortality). The contribution to mortality has remained high as improvements in acute care have contributed to an increase in the median age of the population and as new risk factors, such as diabetes and obesity, have increased. The 2018 Gordon Research Conference (GRC) on Cardiac Regulatory Mechanisms, is the premier conference centered on the fundamental physiological mechanisms that control normal cardiac function and how they are altered by disease, with the goal of discovering novel mechanisms to protect or restore function of the failing, injured or arrhythmic heart. The 2018 GRC, and its integrated Gordon Research Seminar (GRS), organized by and for early career scientists, will focus on how fundamental molecular processes can be leveraged for therapeutic intervention using cutting-edge approaches. The subjects included in the program cover the latest advances in understanding cardiac function/dysfunction in the areas of heart failure, metabolic disease, cardiac signal transduction, cell or gene therapy, regulation by non-coding DNA/RNA, ion transport and myocyte/non-myocyte communication. The main objectives of the GRC/GRS are 1) to disseminate the latest information and technological advances in Cardiac Regulatory Mechanisms pertinent to novel therapeutic interventions for heart disease; 2) to engage and mentor the next generation of basic and physician-scientists in cardiovascular research; and 3) to stimulate collaboration and multidisciplinary communication in inclusive environment unique to the Gordon Research Conferences, which features discussions of unpublished, controversial or paradigm-challenging data.