Monoclonal antibodies (Mabs) offer the potential as useful therapeutic agents because of their high affinity and selectivity for the target antigen. The standard approach in making Mabs has been to immunise rodents, usually mice, with the desired human protein and generate a mouse anti-human IgG through hybridoma technology. Indeed mouse Mabs are used clinically in acute diseases, such as the use of OKT3 (an anti-CD3 Mab) for the treatment of acute rejection episodes following transplantation. The major drawback for these murine Mabs is the high prevalence of anti-mouse antibody responses in the recipient (the so-called HAMA response). This has two consequences: it results in rapid clearance of the Mab and could cause a large immune response if it (or any other murine Mab) was given a second time. Such Mabs are therefore unsuitable for chronic diseases where repeat therapy is required. Immunogenicity can be reduced using human Mabs produced, for example, by phage display or to humanise or CDR graft a mouse antibody. This reduces the number of mouse residues in the Mab to about 12–15%, the vast majority of which are contained in the CDR regions. Such engineered human antibodies are now having a large impact on the treatment of chronic diseases. Although much of the early pioneering work was done with Mabs in different animal systems, the last few years have seen a plethora of clinical studies performed. These advances have resulted in the registration throughout the world of the first of these drugs for a wide range of diseases.