Ethers are abundant in secondary metabolism where they contribute to the structural diversity of polyketide, alkaloid, and terpenoid natural products, 1 yet they are rare in primary metabolism. The ether functionality is similarly popular in traditional organic chemistry due to its stability and ease of construction through alkoxides. However, nature seemingly avoids it for routine uses for precisely those reasons: i) Great stability complicates biological recycling and ii) alkoxide chemistry is difficult to orchestrate in aqueous environments. Thus, biological ethers typically occur only where stability is important or where difficult alkoxide chemistry can be avoided. As such, nature has found a variety of workarounds to make ethers by employing radical coupling, intramolecular substitutions, ring strain-promoted transformations, and Michael additions. To supplement these primarily substrate-dependent transformations, nature uses a small repertoire of general enzymatic transformations to access this functionality. For example, S-adenosylmethionine (SAM)-dependent methyltransferases (using sulfonium chemistry) install aryl methyl ethers as capping groups, for instance in lignin biosynthesis or catecholamine metabolism, and aromatic prenyltransferases (using carbocations) install aryl prenyl ethers on a variety of secondary natural products and peptides. Consequently, there are comparably few enzymes capable of constructing ether bonds in a general fashion. However, enzymatic approaches to this functionality are highly sought after, as they offer solutions to the inherent challenges in traditional ether synthesis: i) Harsh conditions, as alkoxide intermediates typically require the use of strong bases and ii) limited regioselectivity, as multiple hydroxy groups in a given substrate typically possess very similar acidity and reactivity. As such, there is great interest in expanding the toolbox of ether synthases, which can operate under mild, aqueous conditions and with largely unmet regioselectivity. Consequently, tremendous progress has recently been made with biocatalytic alkylations using engineered methyltransferases and SAM-analogues as well as engineered peptide prenyltransferases. In contrast to the wealth of work on these enzyme families, other naturally occurring ether synthases are comparably sparsely researched.