: This review aims to consider retrospectively the available data on the coding propertiesof pri‐microRNAs and the regulatory functions of their open reading frames (ORFs) and the en‐coded peptides (miPEPs). Studies identifying miPEPs and analyzing the fine molecular mechanismsof their functional activities are reviewed together with a brief description of the methods to identifypri‐miRNA ORFs and the encoded protein products. Generally, miPEPs have been identified inmany plant species of several families and in a few animal species. Importantly, molecular mecha‐nisms of the miPEP action are often quite different between flowering plants and metazoan species.Requirement for the additional studies in these directions is highlighted by alternative findings con‐cerning negative or positive regulation of pri‐miRNA/miRNA expression by miPEPs in plants andanimals. Additionally, the question of how miPEPs are distributed in non‐flowering plant taxa isvery important for understanding the evolutionary origin of such micropeptides. Evidently, furtherextensive studies are needed to explore the functions of miPEPs and the corresponding ORFs andto understand the full set of their roles in eukaryotic organisms. Thus, we address the most recentintegrative views of different genomic, physiological, and molecular aspects concerning the expres‐sion of miPEPs and their possible fine functions.