Use of monolithic supports for enzyme immobilization has rapidly expanded since we published the preceding paper in the series of articles concerned with this topic almost three years ago. Many groups worldwide have realized the benefits of applying monoliths as support structures and used a variety of techniques to immobilize many different enzymes. Although some of these new developments are just refinements of the methods developed previously, some notable new approaches have also been reported. This review summarizes the literature published since 2006 and demonstrates the broad variability of reactive monoliths prepared from silica as well as from organic polymers in the form of disks, columns, and capillaries. All these monoliths were prepared by direct formation from reactive precursors or activation of preformed inactive structures. Interestingly, most of the applications of monolithic enzyme reactors target proteolytic digestion of proteins for proteomic analysis.