Chronic graft-versus-host disease (cGVHD) is a major cause for late non-relapse-related death in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), and seriously affects their quality of life. cGVHD may involve many systems in the whole body and its clinical manifestations are similar to autoimmune diseases, and the main pathology is fibrosis. The therapeutic regimen based on glucocorticoids remains as the first-line treatment for cGVHD. Since long-term and high-dose application of glucocorticoids result in serious complications, along with the appearance of steroid-resistant and recurrence/refractory cGVHD, conventional immune suppressive agents have limited clinical efficacy. With the progress in understanding of the pathological mechanisms for cGVHD, many treatments, such as depletion of alloreactive T cells, B-cell depletion, preventing B cell differentiation, targeting the B-cell receptor signaling pathway, inhibition of cytokine receptor-mediated signaling, enhancement of Tregs in vivo, adoptive Tregs therapy, facilitating Tregs reconstitution, and anti-fibrosis therapy, have been supported by clinical and preclinical results.