Monoclonal antibodies (mAbs), which have been essential tools for research use or clinical therapeutics, are often mouse origin. However the mouse system is limited by a small spleen and are usually inbred which leads to a less diversity of immune response. The rabbit has robust immune system and bigger spleen to generate antibodies with high affinity, high specificity and broad immunogenicity. Further, the simpler structure of rabbit immunoglobin makes it easy for cloning, engineering and humanizing of the antibody which benefits therapeutic antibody development. Here we compare differences between mouse and rabbit antibody and outline current approaches to rabbit monoclonal antibody generation.