Antibody-mediated or humoral rejection in combination with development of de novo donor-specific antibodies (DSA) has been recognized as a significant barrier for long term transplant survival and is responsible for one third of the failed allografts. The lung is one of the most susceptible organs for chronic lung allograft dysfunction (CLAD) which affects about 50% of lung transplant patients. There are two different phenotypes of chronic rejection of lung allografts: (1) restrictive CLAD (rCLAD) or restrictive allograft syndrome (RAS), and (2) bronchiolitis obliterans syndrome (BOS). Patients with rCLAD/RAS have a significantly worse survival compared with BOS patients. Newest studies in mouse model establish an obligatory role for DSA (or alloantibody) production by B cells in the allograft fibrogenesis in RAS after lung transplantation. Therefore, a detailed knowledge of the mechanisms that initiate and maintain B-cell driven anti-donor reactivity is required to prevent and better treat alloresponse in lung transplant patients. During recent years, it became clear that alloantibody response largely depends on the actions of follicular helper T (Tfh) cells. In this overview paper, we review the latest insights on the functions of Tfh cells and their roles in antibody-mediated rejection (AMR), and discuss possible strategies of intervention.