Hybridoma fusion technology, proposed by Köhler and Milstein in 1975, started major developments in the field of monoclonal antibodies (mAbs). During the following 2 decades, their high potential as laboratory tools was rapidly exploited for biotechnology and biomedical applications. Today, mAbs represent over 30% of all biological proteins undergoing clinical trials and are the second largest class of biodrugs after vaccines. With the help of antibody engineering, mAbs have been reduced in size, rebuilt into multivalent molecules, and conjugated with drugs, toxins, or radioisotopes for the treatment of cancer, autoimmune disorders, graft rejection, and infectious diseases. Additionally, in the past few years, important advances have been made in the design, selection, and production of these new types of engineered antibodies. The present review focuses on the structural and functional characteristics of mAbs and their fragments, and also provides a walk through the most important methods used in antibody selection. In addition, the recent trends in antibody engineering for improving antibody clinical efficacy are also reviewed.