Allergic rhinitis triggers a systemic increase of inflammation. Within minutes of allergen exposure, immune cells release histamine, proteases, cysteinyl leukotrienes, prostaglandins, and cytokines. Some produce the early symptoms, while others augment the production, systemic circulation, and subsequent infiltration of the nasal mucosa with inflammatory cells that sustain the symptoms. Systemic circulation of inflammatory cells permits their infiltration into other tissues where chemoattractant and adhesion molecules already exist. Consequently, allergic rhinitis is linked to comorbid conditions: asthma, chronic hyperplastic eosinophilic sinusitis, nasal polyposis, and serous otitis media. Effective therapy should be directed at underlying inflammation and its systemic manifestations. It should improve the rhinitis and the comorbid conditions. Antihistamines relieve early symptoms by blocking basophil- and mast cell–generated histamine, but they do not significantly influence the pro-inflammatory loop. They are often little better than placebo. Oral corticosteroids provide the systemic anti-inflammatory efficacy, but their toxicity precludes such an approach. Intranasal corticosteroids effectively target the local inflammatory processes of rhinitis, reducing local inflammatory cells within the nares, but they do not directly access tissues involved in the comorbid conditions. Leukotriene modifiers have both systemic anti-inflammatory effects and an acceptable safety profile.