Human B lymphocytes not only play the critical role in the humoral immunity to generate antibodies, but also equally important to cellular immunity as B lymphocytes can present antigens to T lymphocytes and can release a range of potential immune-regulating cytokines after stimulations. Human immunoglobulin class switch recombination (CSR) in activated B cells is an essential process in the humoral immunity and the process is complicated and tightly controlled by many regulators. The recent genomic and genetic approaches in CSR identified novel genes that were actively involved in the process. Understanding the roles of the novel genes in CSR will bring new insights into the mechanisms of the process and new potential therapeutic targets for immunoglobulin-related disorders such as allergic asthma and autoimmune diseases.