The cornea is the clear tissue at the front of the eye that transmits light to the retina at the back of the eye. The cornea is covered by an epithelium and surrounded by a narrow band of tissue known as the limbus. The limbus has two important roles in maintaining a healthy corneal epithelium. First, stem cells for the corneal epithelium reside at the limbus and not in the cornea. Second, the limbus acts as a barrier separating the clear avascular corneal epithelium from the surrounding vascular conjunctival tissue. A failure of these limbal functions can result in the painful and blinding disease of limbal stem cell deficiency. In this disease, the corneal epithelium cannot be maintained by the stem cells, and the corneal surface becomes replaced by hazy conjunctival tissue. There are many causes of limbal stem cell deficiency, such as burns to the eye, inflammatory diseases, and hereditary diseases. Current understanding of the pathophysiology of the disease is discussed here. In particular, understanding whether the limbal stem cells are lost or become dysfunctional or indeed whether the limbal microenvironment is disturbed is important when developing appropriate management strategies for the disease.