Velandia-Huerto, Cristian A.; Ali M. Yazbeck; Jana Schor and Peter F. Stadler

MicroRNAs are important regulators in many eukaryotic lineages. Typical miRNAs have a length of about 22nt and are processed from precursors that form a characteristic hairpin structure. Once they appear in a genome, miRNAs are among the best-conserved elements in both animal and plant genomes. Functionally, they play an important role in particular in development. In contrast to protein-coding genes, miRNAs frequently emerge de novo. The genomes of animals and plants harbor hundreds of mutually unrelated families of homologous miRNAs that tend to be persistent throughout evolution. The evolution of their genomic miRNA complement closely correlates with important morphological innovation. In addition, miRNAs have been used as valuable characters in phylogenetic studies. An accurate and comprehensive annotation of miRNAs is required as a basis to understand their impact on phenotypic evolution. Since experimental data on miRNA expression are limited to relatively few species and are subject to unavoidable ascertainment biases, it is inevitable to complement miRNA sequencing by homology based annotation methods. This chapter reviews the state of the art workflows for homology based miRNA annotation, with an emphasis on their limitations and open problems.