The immune response to protein-therapeutics (immunogenicity) is an important safety and efficacy concern during drug development and regulation. The potential consequences of immunogenicity range from loss in quality life to a life-threatening situation. Because most protein-therapeutics address serious medical conditions many are approved even if some fraction of the population elicits an immune response. One strategy to circumvent immunogenicity is de-immunization. My presentation will highlight the most recent advances and remaining challenges for de-immunization of protein therapeutics, with a special focus on T cell epitope identification and deletion.