BACKGROUND: Horner's syndrome results from disruption of the sympathetic innervation to the eye anywhere along its three-neuron circuit. It is essential to be familiar with the oculosympathetic pathway, the structures that are in close proximity to it, and the disease processes that may interrupt it when an evaluation is made of an acquired Horner's syndrome, since it may be a manifestation of a life-threatening condition. CASE REPORTS AND DISCUSSION: Four patients with acquired Horner's syndrome resulting from various etiologies are presented. The first case is that of a 41-year-old man with a history of central retinal artery occlusion and Horner's syndrome caused by an internal carotid dissection. The second patient, a 51-year-old man with a Pancoast tumor, initially went to his chiropractor with sympyoms of weakness and pain in the upper extremity. The third case involves a 49-year-old woman with an enlarged thyroid gland. The fourth patient is a 70-year-old man with a history of a stellate ganglionectomy. The sympathetic pathway to the eye, its anatomical correlates, pharmacologic testing, and the systemic diseases that may cause Horner's syndrome are reviewed. CONCLUSION: Familiarity with the sympathetic pathway to the eye and its anatomical relationships enables one to understand the mechanism by which a Horner's syndrome has developed.