The eye is a delicate organ that, along with other tissues such as the testicles and brain, is considered immune-privileged. Immune cells that reside in the eye must create a tolerogenic microenvironment to prevent unwanted aggressive inflammatory reactions that can compromise function. However, the eye is exposed to persistent environmental insult that may overwhelm immune tolerance and result in eye diseases from diverse origins (autoimmune, infectious, and inflammatory). The immune system plays a central role in the different phases of eye diseases, as alterations in immune cells in response to mechanical, chemical, or infectious stimuli initiate and amplify the immune response that lead to ocular tissue damage. Both resident and infiltrating immune cells also actively inhibit the immune response and promote tissue repair. Emerging evidence is leading to a better understanding of how and when lymphocytes, amongst other immune cells, contribute to inflammatory diseases such as dry eye disease (DED). We have compiled literature identifying the presence and participation of lymphocyte subpopulations that modulate DED from studies in both mice and humans. Notably, most mouse studies have relied on desiccant-stress-induced models (non-autoimmune DED), whereas human studies are predominantly in patients with Sjögren’s syndrome (autoimmune DED).