Synthetic thermoplastic polyacetals have a long history dating back to 1912. While polymers with non-cyclic acetal repeat units are typically well soluble and degrade easily at biologically relevant pH values, polycycloacetals have a rigid polymer backbone, resulting in favorable thermal and mechanical properties but are often insoluble and thus challenging to process. In recent years, the degradation behavior and the availability of many building blocks from renewable resources have sparked renewed interest in poly(cyclo)acetals. This review provides a critical overview over the synthetic routes to polyacetals, highlighting where possible the material properties. Direct polyacetalization and polytransacetalization techniques are discussed first, followed by the polymerization of acetal containing monomers and recent ring opening polymerization approaches. Thermoplastic polyacetals show promise in delivery applications but also as bulk materials, where a combination of excellent material properties, a potential for renewable sourcing and degradation as an end-of-life option are of ever increasing importance.