Acute graft versus host disease (GVHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). The diagnosis of acute GVHD is based on strictly clinical criteria and its severity also determined by these criteria. Currently, there is no validated diagnostic blood test for acute GVHD. This review will summarize proteomics approaches to identify biomarkers for GVHD in the plasma with diagnostic, prognostic and predictive value. If successful, these studies could establish a novel biomarker panel that will contribute important information including long term survival, and that may eventually facilitate therapeutic decisions for allogeneic HCT patients.