With the prevalence of pediatric asthma and allergy rising substantially since last mid-century, birth cohort studies starting in pregnancy have been pivotal in identifying prenatal and early life environmental factors that influence risk of these diseases. With these findings, researchers have been able to identify biological mechanisms at play with the eventual goal of engineering tailored interventions to optimize immune system development and decrease the risk of allergic disorders. In this review, we describe the critical role birth cohort studies have played in starting to disentangle the environmental epidemiology and etiology of childhood-onset asthma and other allergic diseases, and how these studies have guided ongoing clinical trials for asthma and allergy prevention. Lastly, we highlight important questions that remain unanswered and potential approaches to help fill these gaps in knowledge.