Ribonucleases III (RNases III) are endoribonucleases that specifically cleave phosphodiester bonds present in double-stranded RNAs (dsRNAs). The RNase III family enzymes can be classified into three subfamilies (Classes 1–3) based on their structure and biological functions. Simple RNases belonging to Class 1 contain two domains: the RNase III domain, characteristic of all members of the RNase III family, and a dsRNA-binding domain. During the course of evolution, the RNase III enzymes have gained additional domains that allowed them to increase affinity for dsRNA substrates, improve the precision of substrate cleavage to generate products of defined length, and, overall, perform more and more complex functions. This way, Drosha (Class 2) and Dicer (Class 3) ribonucleases have appeared. Drosha is a key protein involved in the initiation of microRNA (miRNA) biogenesis in most animal cells by cleaving primary miRNA transcripts into ~70-nucleotide long pre-miRNAs. Dicer processes pre-miRNAs into functional ~21–23-nucleotide long miRNAs. Apart from their apparent function in miRNA biogenesis, ribonucleases Drosha and Dicer are also involved in other cellular pathways, which are dependent or independent of their cleavage activities. These non-canonical functions of Drosha and Dicer are often orchestrated by their accessory domains.