The Declaration of Istanbul is the first document that has been established by the international transplant community that defines and prohibits transplant commercialism and organ trafficking. Its Custodian Group has successfully led various countries to implement legislation against trafficking and commercialism. The question arises, however, whether efforts to prohibit organ trade are realistic and effective. The Declaration differentiates trafficking from commercialism, yet it does not mention how both acts should be approached by policy. Policies that address transplant commercialism work differently from policies that tackle organ trafficking. There is considerable room for improvement in the current prohibitive approach to commercialism and organ trafficking. The Custodian Group and World Health Organization (WHO) should address commercialism by encouraging the expansion of living donation in the same manner as they encourage deceased donation. Furthermore, the Custodian Group and the WHO can improve their strategy to combat organ trafficking by raising awareness for enforcement. To achieve a consistent and effective prohibition of trafficking, legislation and law enforcement must go hand in hand. Ideally, this can best be achieved by close collaboration between the medical field and (international) criminal justice agencies.