Immunotherapy has emerged as an alternative strategy to treat malignancies in addition to conventional radio-and chemotherapy. There has been a plethora of evidence that the immune system is able to control tumor outgrowth and a number of strategies have been put forward to utilize this ability for immunotherapy. However, some of these strategies have not been very efficient and their success has been limited by tumor evasion mechanisms. A promising approach to engage effector cells of the immune system overcoming some of the escape mechanisms has been introduced more than two decades ago. This approach is based on bispecific antibodies. Here we summarize the evolution of bispecific antibodies, their improvement, remaining obstacles and some controversial reports.