Dry eye is a multi-factorial disease of the ocular surface characterised by loss of tear film homeostasis and accompanied by ocular symptoms, in which tear film stability and osmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles. The ocular surface environment is maintained by immune regulation, which fights exogenous and endogenous pathogens while tolerating self-antigens and commensals. The ocular surface immune response involves innate and adaptive mechanisms involving T Helper cells, memory T cells and regulatory T cells. Upregulation of mitogen-activated protein kinase (MAP-K), c-Jun N-terminal kinase (JNK), extracellular signal-related kinase (ERK) and p38 stimulates nuclear factor kappa- beta (NF-Kb) and other inflammatory cytokines (IL-6 [interleukin], IL-1, TNF [tumour necrosis factor] alpha) that cause activation and maturation of APCs. Adhesion of these antigen-presenting cells (APCs) to lymphatic endothelium, differentiation into effector T cells and trans-endothelial migration is mediated by lymphocyte function-associated antigen-1 (LFA-1): intercellular adhesion molecule -1 (ICAM-1). It also recruits activated T cells, causing more endothelial damage and tear dysfunction. Lifitegrast 5.0% is an LFA-1 antagonist: inhibits the binding of ICAM-1 to LFA-1 on the T-cell surface, blocking the T-cell-mediated inflammation, preventing migration and recruitment and averts the progression of the inflammatory response on the ocular surface. Lifitegrast received FDA approval for use in dry eye disease in 2016 and is efficacious in reducing dry eye symptoms and signs in clinical trials. Given its immune-modulatory mechanism of action, it may be efficacious in treating immune-mediated dry eye disease.