CARTs (T-cells with a chimeric antigen receptor) are one of the most innovative and exciting developments in cancer medicine. In August 2018, two novel drugs were approved in the European Union, both for the treatment of relapsed and refractory aggressive lymphoma, one of them also for the treatment of acute lymphoblastic leukemia in children and young adults up to 25 years. In the foreseeable future, further approvals are expected, e.g., in mantle cell lymphoma and multiple myeloma. Clinical trials with new constructs are ongoing in almost all cancer entities. The introduction of this completely new principle implicates unusual challenges: (1) The use of genetically modified “living drugs” is challenging from a regulatory point of view and might require a lifelong surveillance of the patient, (2) companies and authorities make high demands on the quality management at the sites, (3) the price of about 280,000 € for the approved treatments rises new socioeconomic and ethical questions. However, CARTs will change the therapeutic landscape in many cancers in upcoming years.