The prevalence of asthma is increasing in developing countries and the burden of uncontrolled asthma affects patients, families, and the health system. This is to summarize, evaluate, and discuss previous reports on the impact of a targeted and comprehensive approach to the most severe cases of asthma in a low-income setting. A Program for Control of Asthma (ProAR) was developed in Salvador, Bahia, Brazil, prioritizing the control of severe asthma. By facilitating referrals from the public health system and providing proper multidisciplinary but simple management including education and medication, for free, the Program enrolled 2385 patients in 4 reference clinics. They are offered regular follow up and discharged back to primary health care only when asthma control can be maintained without requirement of a combination of an inhaled corticosteroid and a long-acting β2 agonist. ProAR has markedly reduced health resource utilization and decreased the rate of hospital admissions because of asthma in the entire City (2.8 million inhabitants) by 74%. Moderate to severe rhinitis was associated with lack of control of asthma. The average income of the families in the ProAR was US$2955 a year, and they spent 29% of all their income attempting to control the severe asthma of one member, a unbearable expenditure for a low-income family. The ProAR was shown to be cost-effective, reducing costs to the public health system (US$387 patient/year) and the families (US$789 patient/year). In a low-income setting of Brazil, an intervention prioritizing the control of severe asthma was feasible, effective, and reduced costs.