Childhood asthma is not distributed evenly throughout the population, and children who grow up in crowded urban neighborhoods have higher rates of asthma and experience greater morbidity because of asthma. There are several environmental and lifestyle factors associated with urban living that are suspected to promote the development of asthma, particularly in the first few years of life. Collectively, this information suggests the hypothesis that exposure in early life to adverse environmental and lifestyle factors associated with disadvantaged urban environments modifies immune development to increase the risk for allergic diseases and asthma. The Urban Environment and Childhood Asthma (URECA) birth cohort study was initiated in 2004 to test this hypothesis. The study population was recruited prenatally and consisted of 560 families from 4 urban areas who were at high risk for allergies and/or asthma on the basis of parental histories, along with an additional 49 families without atopic parents. Immune development, respiratory illnesses, and exposure to stress, indoor pollutants, microbial products, and allergens were measured prospectively, and the major study outcomes are recurrent wheeze at 3 years of age and asthma at age 7 years. This review summarizes the study design, methods, and early findings of the URECA study.