Cardiovascular diseases (CVDs) are the leading causes of death and disability worldwide, despite the wide diversity of molecular targets identified and the development of therapeutic methods. MicroRNAs (miRNAs) are a class of small (about 22 nucleotides) non-coding RNAs (ncRNAs) that negatively regulate gene expression at the post-transcriptional level in the cytoplasm and play complicated roles in different CVDs. While miRNA overexpression in one type of cell protects against heart disease, it promotes cardiac dysfunction in another type of cardiac cell. Moreover, recent studies have shown that, apart from cytosolic miRNAs, subcellular miRNAs such as mitochondria- and nucleus-localized miRNAs are dysregulated in CVDs. However, the functional properties of cellular- and subcellular-localized miRNAs have not been well characterized. In this review article, by carefully revisiting animal-based miRNA studies in CVDs, we will address the regulation and functional properties of miRNAs in various CVDs. Specifically, the cell-cell crosstalk and subcellular perspective of miRNAs are highlighted. We will provide the background for attractive molecular targets that might be useful in preventing the progression of CVDs and heart failure (HF) as well as insights for future studies.© 2022 Huaping Li et al., published by De Gruyter, Berlin/Boston.