Inner-city children with asthma are known to have high disease mortality and morbidity. Frequently, asthma in this high-risk population is difficult to control and more severe in nature. Several factors, including socioeconomic hardship, ability to access to health care, adherence to medication, exposure to certain allergens, pollution, crowd environment, stress, and infections, play an important role in the pathophysiology of inner-city asthma. Comprehensive control of home allergens and exposure to tobacco smoke, the use of immune based therapies, and school-based asthma programs have shown promising results in asthma control in this population.