Due to the advent of less-toxic reduced intensity conditioning regimens (RIT), allogeneic hematopoietic cell transplantation (allo-HCT) is currently widely used to treat chemotherapy-resistant hematological diseases, particularly in older patients,which are the fastest growing group of patients receiving allo-HCT. However, graft-versus-host disease (GVHD) is still the major complication after allo-HCT, causing immune deficiency, infection, organ damage, and occasionally patient death. Mortality from GVHD is in part attributed to the difficulty in making accurate diagnosis and determining the optimal timing for appropriate treatment. The diagnosis of acute GVHD is dependent on clinical features and is sometimes indistinguishable from other causes and requires invasive procedures. Therefore, non-invasive, diagnostic and predictive monitoring tools, such as plasma/serum biomarkers, are needed. Determination of the roles of cytokines in the physiopathology of acute GVHD has provided an explanation for many preclinical and clinical observations. However, measurement of a single cytokine lacks specificity for GVHD diagnosis. Therefore, comprehensive assessment of plasma/serum cytokine concentrations is required to identify a panel of biomarkers with good specificity and sensitivity for GVHD. In this review, we summarize the roles of individual cytokines in the pathophysiology of acute GVHD and discuss the possibility of cytokines as biomarkers of acute GVHD after allo-HCT.