A growing number of patients with end-stage lung disease have benefited from lung transplantation (LT). Improvements in organ procurement, surgical techniques and intensive care management have greatly increased short-term graft survival. However, long-term outcomes remain limited, mainly due to the onset of chronic lung allograft dysfunction (CLAD), whose diagnosis is based on permanent loss of lung function after the development of irreversible lung lesions. CLAD is associated with high mortality and morbidity, and its exact physiopathology is still only partially understood. Many researchers and clinicians have searched for CLAD biomarkers to improve diagnosis, to refine the phenotypes associated with differential prognosis and to identify early biological processes that lead to CLAD to enable an early intervention that could modify the inevitable degradation of respiratory function. Donor-specific antibodies are currently the only biomarkers used in routine clinical practice, and their significance for accurately predicting CLAD is still debated. We describe here significant studies that have highlighted potential candidates for reliable and non-invasive biomarkers of CLAD in the fields of imaging and functional monitoring, humoral immunity, cell-mediated immunity, allograft injury, airway remodeling and gene expression. Such biomarkers would improve CLAD prediction and allow differential LT management regarding CLAD risk.