Structures that have been elusive for decades are now being determined using Cryogenic electron microscopy (cryo-EM). Our group has determined cryo-EM structures of two RNA polymerase (RNAP) complexes from the bacterium Bacillus subtilis, and two DNA annealase complexes from a bacteriophage and a human virus. Comparison of the two RNAP structures, one with and the other without the HelD factor that removes stalled RNAP complexes from DNA, allowed us to propose a molecular mechanism for HelD’s action (1). Our phage lambda annealase structure had been sought after for more than half a century. This structure revealed the unusual DNA structure formed by this protein to enable the search for the correct base-pairing during single-strand annealing (SSA) homologous DNA recombination. It also shows how this protein forms large helical structures to accommodate long DNA molecules (2). Furthermore, this structure helped in conclusively establishing a new protein superfamily, bringing a decades-long hypothesis discussion in the field to a close, in addition to helping define a new protein fold (3). Our second annealase structure, obtained from a Human Herpes Virus, reveals entirely different mechanisms employed by these viruses to form long helical assemblies and promote DNA annealing (manuscript in prep).