Keratoconus is a disease of the cornea that results in progressive steepening and thinning of the cornea and subsequent vision loss. It nearly always presents as a bilateral disease, suggesting that there is an underlying abnormality of the corneas that becomes manifest with time. However, the mechanisms underlying the development of keratoconus are largely unknown. Associations reported between keratoconus and systemic diseases are abundant in the literature, and the list of possible associations is very long. We found that atopy, Down syndrome, and various connective tissue diseases were the most frequently cited associations in our broad literature search. Additionally, Diabetes Mellitus has been increasingly studied as a possible protective factor against keratoconus. In this review, we have summarized the evidence for and against these particular systemic conditions and keratoconus and have discussed some of the implications of keratoconus patients having these conditions.