Chronic graft-versus-host disease (GvHD) remains a significant cause of late morbidity and mortality following allogeneic stem cell transplantation. However, patients with chronic GvHD are very heterogeneous, making evaluation and treatment difficult. Corticosteroids remain the most effective primary treatment of this condition. Randomized trials have not confirmed the beneficial effect of additional cyclosporine, even in patients with higher risk features. For patients failing initial therapy, no standard therapy is available. A plethora of drugs have been reported to have activity and promise in this disease. However, the majority of reports are small retrospective studies, with few prospective trials. The marked variability in the reported response rates for many of these novel agents highlights a number of problems in the evaluation and management of chronic GvHD. In addition to the heterogeneity of patients, there are no uniform definitions for treatment failure, prognostic criteria to stratify patients according to risk, or to evaluate response to treatment, which in many cases is largely subjective. The challenge ahead is to develop more uniform criteria for defining many of these important variables, which is likely to lead to the design of better prospective clinical trials to improve the outcome of patients with this condition.