MicroRNAs are transcribed from primary transcripts that have all the characteristics of mRNAs (for example, transcription by RNA polymerase II, splicing, 5’ cap, 3’ polyadenylation) [1]. Using expression evidence and sequence signals, we have annotated over 50 primary microRNA transcripts in mammals [2]. We find that many are between 1 and 10 kilobases in length, and a handful are hundreds of kilobases long, even though the final functional products are around 22 bases. Genomic and computational approaches show that microRNA transcripts often make multiple products, both protein and RNA. Around half of all mammalian microRNA transcripts are also protein-coding mRNAs, with microRNAs contained in intronic sequence [3]. In the general case, the protein-coding transcript and the microRNA appear to be co-transcribed. MicroRNAs may be transcribed polycistronically, with multiple microRNA hairpins excised from a single transcript [1]. The relationship between multiple clustered microRNAs, and intronic microRNAs and their protein-coding hosts are conserved in related genomes. A single microRNA hairpin precursor can also make functional mature products from one or both arms. Usually, a mature sequence from one arm dominates; a low abundance sequence from the opposite arm (called the miR* sequence) is also often detected in high-throughput sequencing experiments. We show that the oldest extant microRNA family, the mir-100/10 family, has undergone at least four independent evolutionary events that have switched the arm from which the dominant functional microRNA is processed. For example, the dominant miR-10 sequence in D. melanogaster is processed from the 3′ arm of the precursor, whereas the dominant mammalian miR-10 sequence is excised from the 5′ arm. A high-throughput sequencing experiment in the flour beetle T. casteneum shows that around 10% of microRNAs that are conserved between fly and beetle have switched the arm that makes the functional product, including the mir-10 sequence. The sequences from opposite arms of the hairpin are not similar, and therefore their predicted mRNA targets differ significantly. Arm switching is therefore general, and the functional consequences are profound. Expression of fly and beetle mir-10 sequences in Drosophila S2 cells provides insight into the mechanisms of arm choice. In general, microRNA transcripts may produce multiple products: protein-coding transcript and intronic microRNA; multiple clustered precursor hairpins processed from a single transcript; and two mature microRNA processed from opposite arms of the precursor hairpin. The functional relationship between multiple products from the same locus is unclear, but this question is amenable to computational and genomic analysis.