Abstract Purpose of the Review Cardiovascular disease remains the leading cause of death worldwide, resulting in cardiac dysfunction and, subsequently, heart failure (HF). Single-cell RNA sequencing (scRNA-seq) is a rapidly developing tool for studying the transcriptional heterogeneity in both healthy and diseased hearts. Wide applications of techniques like scRNA-seq could significantly contribute to uncovering the molecular mechanisms involved in the onset and progression to HF and contribute to the development of new, improved therapies. This review discusses several studies that successfully applied scRNA-seq to the mouse and human heart using various methods of tissue processing and downstream analysis. Recent Findings The application of scRNA-seq in the cardiovascular field is continuously expanding, providing new detailed insights into cardiac pathophysiology. Summary Increased understanding of cardiac pathophysiology on the single-cell level will contribute to the development of novel, more effective therapeutic strategies. Here, we summarise the possible application of scRNA-seq to the adult mammalian heart.