Mucormycosis is a rare fungal infection that can involve the sino-orbito-cerebral region. Sino-orbito-cerebral mucormycosis is most common in patients who are immunocompromised or have diabetes mellitus, severe malnutrition or burns. This condition can be fatal if it is not diagnosed early and treated aggressively. This article presents 4 cases of mucormycosis, including 2 with orbital apex syndrome, 1 with cavernous sinus syndrome, and 1 with multiple cranial nerve involvement. All of the patients were presented with painful ophthalmoplegia. The predisposing factors for mucormycosis included diabetes mellitus (three patients) and chronic leukemia (one patient). In all cases, mucormycosis was diagnosed by examining endoscopic sinus drainage material and was treated with surgical debridement and amphotericin B. Two patients with central nervous system involvement died. The others have survived, but still exhibiting various neurologic abnormalities after aggressive treatment. Patients with mucormycosis rarely present with orbital apex syndrome. The possibility of mucormycosis should be investigated in any patient with painful ophthalmoplegia, and prompt otorhinolaryngologic examination is recommended to ensure rapid diagnosis and treatment.