Getting higher yields of monoclonal antibody (MAb) is a problem in Hybridoma Technology which has two major bottlenecks: a) poor yield of hybridized cells, b) low cellular productivity of MAb in culture. There are three ways of obtaining high MAb yield in vitro a) Large scale culture, b) high density culture and c) enhancing individual cellular productivity in culture. Currently, the focus is on the correct synergistic combination of fortified nutrient media, bioreactor design and mode of operation. Maximization of cell culture longevity, maintenance of high specific antibody secretion rates, nutrient supplementation, waste product minimization and control of environmental conditions are important parameters for improvement of large scale production of MAb. Though, MAb yields have improved rapidly over the decade, there is a growing concern for the decrease in quality of MAb secreted. Further research is therefore necessary to take full advantage of MAb as a potential diagnostic agent for in vivo therapy.