Given the various ocular manifestations of limbal stem cell insufficiency, an awareness of the genetic, acquired, and immunological causes and associated additional treatments of limbal stem cell deficiency (LSCD) is essential for providers. We performed a comprehensive review of the literature on the various etiologies and specific therapies for LSCD. The resources utilized in this review included Medline (PubMed), Embase, and Google Scholar. All English-language articles and case reports published from November 1986 through to October 2022 were reviewed in this study. There were collectively 99 articles on these topics. No other exclusion criteria were applied. Depending on the etiology, ocular manifestations of limbal stem cell deficiency range from dry eye syndrome and redness to more severe outcomes, including corneal ulceration, ocular surface failure, and vision loss. Identifying the source of damage for LSCD is critical in the treatment process, given that therapy may extend beyond the scope of the standard protocol, including artificial tears, refractive surgery, and allogeneic stem cell transplants. This comprehensive review of the literature demonstrates the various genetic, acquired, and immunological causes of LSCD and the spectrum of supplemental therapies available.