The eye is often the first organ involved in systemic diseases. An ophthalmologist may see an initial ocular manifestation of an ocular disease, or the eye may get involved along the course of a systemic disease and/ or its management. It is important for a clinician not only to know the systemic associations of ocular conditions but also to monitor the eye in systemic conditions where it can get involved—case in point being metabolic diseases like diabetes and thyroid dysfunction. Through this chapter we provide a review of congenital and acquired conditions ranging from autoimmune and connective disorders to cutaneous disorders where the eye can harbor features.