The ability to produce antibodies that are directed against specific antigens has played a crucial role in advancing scientific discoveries. Recombinant technologies have extended the application of antibodies beyond the research laboratory and into the clinic for the treatment of cancer and other diseases. Creative approaches using these technologies have been used to reduce the antibody to its minimal functional size, and/or make them bifunctional (immunotoxins), bispecific, or less immunoreactive (humanized). Additionally, mice that are engineered to generate antibodies of human genomic origin have been used to produce therapeutic antibodies and are being further developed. As the research and clinical demands for antibodies continue to increase, the development of improved resources (cell lines and animals) to improve production efficiency, generate larger repertoires, and deliver greater yields of antibodies is being explored, and advances in this area are discussed further in this review.