The development of antibody catalysts and indeed natural antibody responses has in the past been based on non-covalent binding to antigens. In contrast to this, reactive immunization utilizes reactive immunogens that covalently react with antibodies during the course of their induction through a designed chemical transformation. The inducing chemical transformation is designed to become part of the catalytic mechanism when the antibody is subsequently challenged with substrate molecules. Reactive immunization has proven to be an efficient approach to generating highly proficient catalytic antibodies with unusually broad substrate scope. This review describes catalytic antibodies generated by reactive immunization, their features and applications, as well as in vitro selection of catalytic antibodies based on reactive compounds.