Non-specific enzyme therapy does not intend the catalysis of definite steps of metabolism, but claims to stimulate regenerative processes in general. Initially, non-specific enzyme therapy had been considered to be a promising approach. The growing knowledge in basic research and the lack of evidence for clinical effectiveness rendered the predominantly oral application of enzyme preparations for non-specific treatment outdated by the 1960s. In Germany, however, the absence of strict legal regulations prevented the deregistration of drugs designed for non-specific enzyme therapy. Furthermore, numerous clinical studies were initiated by the leading producer of enzyme preparations in Germany in order to provide the scientific confirmation missing so far. Our critical and systemic review of the published trials shows that neither the mechanism of action could be enlightened, nor the clinical benefit of non-specific enzyme therapy proven on an acceptable level of scientific standards.