Casein kinase 2 (CK2) is a highly conserved serine–threonine kinase that uses both adenosine triphosphate and guanosine triphosphate as phosphate donors. This constitutively active and ubiquitously expressed enzyme is often present as a tetrameric holoenzyme complex of two catalytic subunits (α and/or α’) and two regulatory β subunits. The enzyme is known to phosphorylate more than 300 substrates and controls a wide range of processes, including the regulation of cell cycle, apoptosis, transformation, and circadian rhythm. Several lines of recent evidence also suggest a potentially important role for CK2 in the control of the inflammatory response. This review will give an overview of CK2 and its regulation and describe the evidence implicating its role in inflammation.