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Advances over the past fifty years in the field of vaccination and the exploration of the immune response offer positive prospects for the prevention of infectious diseases. However, there is still a long way to go to improve the efficacy and safety of vaccination for transplant recipients or immunocompromised patients in the broad sense. In these populations, the benefit/risk balance of vaccination is even more pronounced in favor than that of the general population. Thus, consistently generating data in these populations is of great importance but can be disrupted by various human, technical, and financial factors. In this article, we will attempt to describe some of these limitations for the immune response to vaccination and its exploration, especially in transplant recipients.