Aspergillosis of head and neck region primarily affects the nose and paranasal sinuses. Any type of paranasal aspergillosis may progress to more aggressive disease illustrating the importance of early recognition of this increasingly encountered disease. The invasive and in particular, the fulminant forms are associated with high mortality. We report a case of invasive aspergillosis of right maxillary sinus and orbit in an immunocompetent individual, along with a critical review and update of the literature. The patient underwent surgery for the debridement of right maxillary sinus through a Caldwell-Luc approach and drainage of orbital abscess as well followed by intravenous therapy of amphotericin B. Recovery with reduction of all the signs and symptoms was seen after 38 days from the appearance of first symptoms. Successful treatment of aspergillosis requires prompt diagnosis and rapid institution of therapy, because delay or nonaggressive therapy can result in the spread of infection with lethal consequences. How to cite this article Neeli AS, Kotrashetti SM, Vallavan P. Sino-orbital Aspergillosis: A Case Report and Brief Review of Literature. World J Dent 2012;3(4):363-366.