Patients who receive a solid organ transplantation (SOT) or a stem cell transplantation (SCT) require immunosuppressant drugs to suppress the patients’ immune response to the transplant and prevent rejection of the transplant. The goal with immunosuppression is to induce donor specific tolerance for the transplant with minimal impairing of the patients’ defenses or increasing the susceptibility to infections. The most common immunosuppressants prescribed are the calcineurine inhibitors cyclosporine and tacrolimus, and the mTOR inhibitors sirolimus and everolimus. These immunosuppressants are used for the prophylaxis and treatment of graft rejection following SOT (kidney, lung, hart, and liver) and SCT. With cyclosporine, tacrolimus, sirolimus, and everolimus, clinical variability due to inter- and intra- patient pharmacokinetic variability is seen. This pharmacokinetic variability, in combination with an excellent correlation between blood concentrations and efficacy/toxicity of the treatment and the narrow therapeutic range of the immunosuppressive drugs, makes monitoring of blood concentrations a crucial part of the treatment. The therapeutic range for each immunosuppressant drug depends on post-transplant time, concomitant immunosuppressive medication, and immunological risk.