Systemic acute rhinosinusitis therapy consists mostly of antibiotic treatment because pathogens play a major role. Amoxicillin is the drug of choice for treatment of acute rhinosinusitis, with second- and third- generation cephalosporins, azythromycin, clarithromycin, and telithromycin as possible options, especially in the case of allergy to amoxicillin. If the clinical course suggests that an anaerobic pathogen is more likely, clindamycin or metronidazole can be considered in combination with a broad-spectrum drug. In antimicrobial treatment of chronic sinusitis there is no consensus on treatment length, organism coverage, or which antibiotics are most effective because the bacteriology is variable with polymicrobial anaerobic and aerobic organisms present. Adjuvant therapies need to be proven by additional studies. Chronic rhinosinusitis is heterogeneous and treatment should vary according to the causative factor involved. Short courses of systemic steroids have been found very useful to decrease mucosal swelling and inflammation in chronic rhinosinusitis. However, no randomized controlled studies have been performed to validate their efficacy in children. A variety of other agents are used in the treatment of chronic rhinosinusitis including antihistamines, decongestants, and leukotriene modifiers. To date, there is no good evidence from randomized controlled studies to support the use of any of these agents in the treatment of this disease in either children or adults.