A variety of systemic pathological processes may involve the eye and the surrounding orbital adnexae. CT and MRI of the orbit have become useful clinical adjuvants, not only in establishment of the diagnosis, but also in suggesting the appropriate clinical treatment, sometimes preventing needless biopsy. Grave's disease, Wegener's granulomatosis, and sarcoidosis may all present initially with orbital disease before the onset of systemic manifestations. Idiopathic inflammatory disease of the orbit and lymphoproliferative disease of the orbit continue to remain radiological and clinical challenges. The article discusses the CT and MRI appearance of many of the common systemic diseases in adults with attention to features useful in clinical practice as well as in differential diagnosis.