Generic immunosuppressive drugs are available in Europe Canada and the United States. Between countries, there are large differences in penetration of generic drugs in general, and for immunosuppressive drugs in particular. The registration for generic immunosuppressive drugs are slightly different, but the criteria for registration of narrow therapeutic index drugs and bioequivalence studies, performed only in healthy volunteers, will remain in the medical landscape. About 50 studies compare the clinical eficacy and bioequivalence of the generic immunosuppressive drugs in patients with solid organ transplants. To allow for safe substitution, a number of criteria need to be fulfilled. Consensus statements were made by most transplant organizations. Authorities and payers should refrain from forcing pharmacists to dispense generic drugs in patients on maintenance immunosuppressive treatment. Generic substitution could be safe if realized by the treating physician, for a well-informed patient. Substitution must be followed by control visits to check if the patient is taking the medication correctly and if the drug exposure, through a close monitoring, remains stable. Substitution from one generic to another generic should be avoided, in all cases.