The differential diagnosis of unilateral sinus disease (USD) is broad, and while concerning etiologies like sinonasal neoplasia, invasive fungal sinusitis, and cerebrospinal fluid rhinorrhea should always be considered, most cases are due to noninvasive inflammatory or infectious conditions. To diagnose USD appropriately, clinicians must integrate the clinical history and examination, nasal endoscopy, computed tomography (CT), and possibly MRI. Odontogenic sinusitis (ODS) is the most common cause of unilateral maxillary sinus opacification on CT, with 45% to 75% of such cases being odontogenic in nature. This study provides USD diagnostic considerations and reinforces the diagnostic approach to ODS.