Antibodies are critical components of the adaptive immune system, whose therapeutic applications have been growing exponentially in the last years. Discovery and development of therapeutic antibodies encompasses in vivo immunization, synthetic libraries, and surface display methodologies. To overcome some of their limitations, several platforms in higher eukaryotic cells have been developed. Moreover, these platforms aim to replicate in the bench both primary and secondary antibody diversification mechanisms that occur in vivo. Here, we describe the latest strategies that have been used to mirror both naive and affinity-maturated antibody repertoire.