The sclera forms the outer coat of the eyeball. Diseases affecting the sclera can be classified as congenital, metabolic, degenerative, inflammatory, and infective. Diseases of the sclera are often not encountered in isolation, but they can be. They are usually a continuation of a disease process from a contiguous structure like the cornea or the uvea, or a manifestation of an underlying systemic disease. It is important to evaluate patients with scleral disease for systemic conditions, as a scleral manifestation may be the first sign of a more sinister pathology. In many instances, the attributes of a scleral pathology may be sufficiently characteristic to diagnose a systemic pathology. Scleral inflammation or scleritis can be due to infectious or noninfectious causes, and it is paramount to differentiate between the two; as antimicrobial agents are the mainstay for infectious causes, whereas immunosuppressive drugs are the treatment of choice for immune-mediated causes. The use of immunosuppressives in infectious scleritis due to missed etiology can lead to worsening. In this chapter, we will discuss the embryological derivation of the sclera, congenital conditions, commonly encountered metabolic diseases of the sclera, scleritis—infectious and noninfectious, and degenerative conditions such as plaque and phthisis bulbi.