Using immunotherapy to fight cancer, and specifically, the use of engineered T-cells expressing a chimeric receptor against an antigen found on malignant cells (chimeric antigen receptor, CAR-T cells) constitutes a significant breakthrough in the treatment of the disease. In recent years, several CAR-T therapies have been approved in Europe and the USA, and some are already approved and funded through the national health basket in Israel, for the indications of diffuse large B-cell lymphoma, mantle cell lymphoma and B-cell acute lymphoblastic leukemia, after the failure of at least two lines of treatment. The treatment with CAR-T cells achieves prolonged remissions and even long-term cure of patients who had a very poor prognosis. However, the treatment involves significant side effects, and requires specific expertise in the management of patients both during the period of preparation for cell transplantation, and following the treatment. During the immediate post-infusion period, the most common adverse reactions are cytokine release syndrome (CRS) which stems from the activation of the immune system, and neurological toxicity that can accompany CRS. These effects require close monitoring, grading their severity, and providing anti-cytokine therapy or steroid therapy until control of symptoms is achieved. Later effects can be persistent cytopenias, immune over-activation, and prolonged immune deficiency. Treatments for additional indications and new CAR-T constructs are being developed and will allow more effective and safer treatment. This article summarizes the principles for CAR-T administration that, as currently provided in Israel, include the short- and long-term follow-up of the patients.