Graft-vs-host disease (GVHD) remains a key limiting factor in the success of hematopoietic stem cell transplantation (HSCT). One of the key cytokines known to have a role in the pathogenesis of GVHD is interleukin-1 (IL-1). The IL-1 gene family consists of 10 members, of which 3 genes encode for the proteins IL-1a, IL-1ss and IL-1Ra (IL-1 receptor antagonist). Polymorphisms in these genes have been associated with variability in the production of the respective cytokines and have been implicated in patient susceptibility to inflammatory diseases, including GVHD. A number of reports have detailed genetic associations between members of the IL-1 gene family and HSCT outcomes. Despite these encouraging reports, a simple exploitation of these findings is probably naive. Differences in transplant practice between centers and within centers over time mean that directly comparable studies are rare. This combined with the complexity of IL-1-related transplant biology means that our understanding of this topic remains limited. This review details the current state of knowledge of IL-1 genetics and transplantation and discusses these issues in the context of the changing practice of transplantation.