This chapter discusses antibiotic therapy in rhinosinusitis, where role of antibiotic therapy for the various forms of rhinosinusitis has evolved in concert with developments in basic science and clinical research. Treatment of sinusitis includes not only antibiotic therapy to reduce the colony counts of the pathogenic bacteria but also anti-inflammatory therapies to restore normal sinonasal physiology. Antibiotics are a mainstay of treatment for CRS since it is believed that the continuous inflammation of this disease process is in part due to a chronic infection that has not been sufficiently eliminated. Antibiotic treatment should take into account patient age and comorbidities. Medical management focuses on decreasing mucosal inflammation, restoring normal sinus physiology, and removing inciting factors, which include infectious organisms. In the majority of patients, surgical intervention for CRS is indicated only after failed medical management. Pain can be treated with nonsteroidal anti-inflammatory drugs, acetaminophen or opioid medication, depending on the severity.