As the first monoclonal antibodies were produced in 1975, the challenge to improve antibody engineering started. Since then, therapeutic antibodies have become the predominant class of new drugs developed in recent years and an essential part of progress has affected cell lines. From the first pioneer hybridoma cells to the current vanguard Chinese hamster ovary [CHO] cells dramatic improvement has been seen. An essential part of this process is choosing the suitable cell line to seed the targeted antibody gene. This review encompasses all the current evidence to compare various types of suitable cell lines for monoclonal antibody production such as mammalian cells, plant cells, bacterial cells, and yeast cells. Valid long-term data, regarding glycosylation, efficiency, and safety, support the current popularity of Chinese hamster ovary [CHO] cells. At the same time, other types of cell lines also show some promise for emerging needs for more therapeutic antibodies on the market.