Hematopoietic stem cell transplantation (HSCT)/bone marrow transplantation (BMT) has become a central treatment modality in the management of various hematologic malignancies, but it is not without treatment sequelae. The major complication of HSCT/BMT is acute or chronic graft-versus-host disease (GVHD). GVHD is an immunologically mediated disease that contributes substantially to transplant-related morbidity and mortality. The overall incidence of GVHD remains between 30% and 60% and carries approximately a 50% mortality rate. Acute and chronic GVHD are complex clinical phenomena. This paper focuses on our current clinical understanding of GVHD as a multiphase process intricately linked to the immune response between the donor (graft) and recipient (host). Based on this complex pathophysiology, clinical nursing care is targeted at the various body systems affected by either acute or chronic GVHD. The article concludes with advances and clinical trials underway that have the potential to reduce the symptomatology of GVHD.