Onodi cells are posterior ethmoid cells superolateral to thesphenoid sinus that is intimately associated with the optic nerve. Embryologically, they are derived from ethmoid cells that have undergone dedifferentiation. The anatomic relationship of the Onodi cell to the optic nerve and the internal carotid artery has not been clearly documented in the literature. Fortyfour sagittal sections of cadaver heads and 83 CT scans of the sinuses were examined. Case studies of three patients with Onodi cell sinusitis are presented. Two patients underwent endoscopic sinus surgery, and the other chose conservative medical management. The cadaver specimens revealed Onodi cells in 14% (6/44 sections). They were located lateral, superior, or superolateral to the sphenoid sinus. These relationships were further delineated by studying CT scans of the sinuses of 76 patients. Six patients (8%) had Onodi cells. Four of them had a dehiscence of the optic nerve adjacent to the Onodi cell. Twelve patients (16%) demonstrated a dehiscence of the internal carotid artery. These findings have important implications in endoscopic sinus surgery. The anatomic variability of the posterior ethmoids, sphenoid sinus, internal carotid artery, and optic nerve makes this surgical approach particularly challenging.