This chapter reviews adenylylsulfate (APS) reductases from sulfate-reducing bacteria (SRB). The sulfate molecule is inert chemically and must be activated in order to enter any of the pathways. All the organisms that utilize sulfate contain the enzyme ATP-sulfurylase, which catalyzes the formation of adenylylsulfate and inorganic pyrophosphate (PPi) from ATP and sulfate. The APS molecule has twice the energy of the comparable ADP molecule, and the equilibrium of the reaction lies in the direction of ATP and sulfate. An inorganic pyrophosphatase shifts the equilibrium toward APS formation by hydrolyzing the PPi molecules. The key reaction in assimilatory sulfate reduction that differentiates it from dissimilatory sulfate reduction is the transferring of the sulfonate group of APS or 3′-phosphoadenosine 5′-phosphosulfate (PAPS) to a thiol group producing the corresponding nucleotide (AMP or PAP) plus a thiosulfonate. This thiol is either a low molecular weight compound such as glutathione or a protein such as thioredoxin or glutaredoxin. The purification of APS reductase must be carried out in such a way that it maximizes its final purity and yet minimizes the time required to accomplish it.