Dnmt2 is a member of the animal DNA methyltransferase family of enzymes. While the role of other Dnmt proteins has been extensively characterized, comparably little is known about Dnmt2. This is surprising because Dnmt2 is the most widely conserved Dnmt protein, with homologues in protists, plants, fungi, and animals. In this review, we discuss the evidence supporting the seemingly contradictory roles of Dnmt2 in both DNA and RNA methylation. New studies are uncovering the enzymatic mechanisms that mediate these activities and also provide first insights into the biological functions of Dnmt2. Lastly, we also discuss observations that suggest a possible role for Dnmt2 in human health and disease, which further emphasizes the importance of defining Dnmt2-modulated cellular pathways in future studies.