Patients undergoing haematopoietic stem cell transplantation (HSCT) are highly exposed to infectious agents. However, it is not known why certain HSCT recipients rapidly develop severe infections while other, despite similar immunosuppressive conditions, do not. Increasing evidence suggests that such differences may be due, in part, to polymorphisms in immune genes. Thus, the identification of genetic factors influencing susceptibility to infections in HSCT recipients may lead to the development of individualized management strategies. However, studies are challenged by several issues, including the relative small size of existing cohorts, the frequent use of prophylactic or preemptive antimicrobial agents, and the fact that genes responsible for immune functions can be inherited either from the donor or the host. Consequently, the major challenge for today's researchers is to overcome these limitations and find associations that are robust enough to be translated into reliable risk stratification strategies for infectious diseases.