Catalytic activity can arise by natural means in antibodies. Several naturally-occurring peptides and synthetic protease substrates are known to be cleaved by antibodies. There is an increased production of antigen-specific catalytic antibodies in autoimmune disease. Antibody light chains isolated from multiple myeloma patients frequently express proteolytic activity. Immunization protocols using as antigens the ground state of a naturally-occurring polypeptide, transition state analogs or anti-enzyme antibodies are known to provoke catalytic antibody synthesis. Active site residues in the light chain subunit serve as the catalytic residues in an antibody with peptide bond cleaving activity. Mutagenesis in the active site can potentially generate improved catalysts. The possible mechanisms underlying proteolysis by natural antibodies and evolution of the catalytic activity are reviewed.