Many pathogens present in the human environment, in immunocompromised patients, can cause extremely severe opportunistic infections. Most patients suffering from immunological disorders are rarely treated at maxillo-facial departments. In some special cases they require a direct clinical approach. Fungal infections in the cranio-facial area do not occur often, as opposed to infections from bacterial flora which are most frequently found. Some special conditions and requirements are needed to be present for the occurrence of fungal infections. If found, many of them are treated locally by antifungal medicaments, while a few of them require additional radical surgical excisional approach. Mucor sp. is one of these infections and it is related with mucormycosis (zygomycosis). Rhinocerebral zygomycosis is particularly dangerous. This rare cranio-facial infection is a great challenge for all clinicians and surgeons. It seems that only an accurate and proper diagnosis has an impact on the patient’s survival and post-treatment quality of life. In this paper we focus on recent clinical findings and treatment methods of this disease.