Progressive cell loss due to apoptosis is a pathological hallmark implicated in a wide spectrum of degenerative diseases such as heart disease, atherosclerotic arteries and hypertensive vessels, Alzheimer’s disease and other neurodegenerative disorders. Tremendous efforts have been made to improve our understanding of the molecular mechanisms and signaling pathways involved in apoptosistic cell death. Once ignored completely or overlooked as cellular detritus, microRNAs (miRNAs) that were discovered only a decade ago, have recently taken many by surprise. The importance of miRNAs has steadily gained appreciation and miRNA biology has exploded into a massive swell of interest with enormous range and potential in almost every biological discipline because of their widespread expression and diverse functions in both animals and humans. It has been established that miRNAs are critical regulators of apoptosis of various cell types. These small molecules act by repressing the expression of either the proapoptotic or antiapoptotic genes to produce antiapoptotic or proapoptotic effects. Appealing evidence has been accumulating for the involvement of miRNAs in human diseases associated with apoptotic cell death and the potential of miRNAs as novel therapeutic targets for the treatment of the diseases. This editorial aims to convey this message and to boost up the research interest by providing a timely, comprehensive overview on regulation of apoptosis bymiRNAs and a synopsis on the pathophysiologic implications of this novel regulatory network based on the currently available data in the literature. It begins with a brief introduction to apoptosis and miRNAs, followed by the description of the fundamental aspects of miRNA biogenesis and action, and the role of miRNAs in regulating apoptosis of cancer cells and cardiovascular cells. Speculations on the development of miRNAs as potential therapeutic targets are also presented. Remarks are also provided to point out the unanswered questions and to outline the new directi