Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule that elicits a number of cytoprotective effects in mammalian species. H2S was originally considered toxic at elevated levels, but 15 years ago the labile molecule was discovered in mammalian tissue and termed a gasotransmitter, thus opening the door for research aimed towards understanding its physiologic nature. Since then, novel findings have depicted the beneficial aspects of H2S therapy, such as vasodilation, antioxidant upregulation, inflammation inhibition, and activation of anti-apoptotic pathways. These cytoprotective alterations effectively treat multiple forms of cardiac injury at the preclinical level of research. The field has progressed towards instituting novel H2S donors that prove more effective at activating the subsequent cardioprotective enhancements over longer time periods. As more findings explore the efficacy of H2S, research focused on detection of sulfhydrated targets is on the rise. Understanding the molecular mechanisms that stem from H2S treatment may lead the field towards powerful therapeutics in the clinical setting. This review will discuss the cytoprotective and cardioprotective effects of H2S therapy, provide analysis on the molecular alterations that lead to these enhancements, and explore recently developed therapeutics that may bring this gasotransmitter into the clinic in the near future.