The potential of antibodies as magic bullets for curing disease has excited the imagination of medical researchers ever since this phrase was first coined by Paul Ehrlich about a century ago. Seventy-five years after the publication of Ehrlich's side-chain theory to explain antibody-antigen reactions in 1900, Georges Köhler and César Milstein invented a means of cloning antibodies with defined specificity that paved the way for major advances in cell biological and clinical research. They were awarded the Nobel Prize in Medicine in 1984 for this ground-breaking research. In 1986, the first monoclonal antibody, the murine mAb OKT3 for preventing transplant rejection, was approved for clinical use, and although many other murine mAbs were subsequently investigated as therapeutic agents, most of them had a disappointing clinical profile largely due to their immunogenicity. This situation improved dramatically with the advent of techniques to humanize existing mAbs, followed by technologies that sought to imitate the generation of specific antibodies by the immune system in vitro. For example, the expression of antibody fragments in E. coli using bacterial leader sequences and the use of phage display and later ribosome display facilitated the selection of specific human antibodies from extremely large libraries. The process of somatic hypermutation to increase antibody affinity was mimicked by introducing random mutations. Another major advance for obtaining human antibodies was the creation of transgenic mice carrying a large part of the human antibody gene repertoire, which could be used to produce human antibodies by standard hybridoma technology.