Chronic sphenoid rhinosinusitis (CSR) recalcitrant to medical and surgical therapy may result from advanced chronic infectious or inflammatory disease, anatomic factors, or inadequate initial surgical/postoperative management of primary chronic sphenoid rhinosinusitis. It is often multifactorial [1]. Persistent inflammatory disease in the sphenoid more commonly results from systemic factors leading to sphenoid sinusitis in the setting of chronic pansinusitis (Fig. 6.1) and occasionally from local factors resulting in isolated chronic sphenoid rhinosinusitis (Fig. 6.2).