There has been a dramatic increase in the prevalence of asthma over the last quarter century, particularly in the industrialized world. Although our understanding of asthma continues to improve, there is no cure for the disease. Primary prevention of asthma is the focus of this review. Asthma is a disease with multiple gene-environment interactions. Candidate genes for asthma are considered, and potential interaction between one of those genes, CD14, and an environmental factor, endotoxin, is reviewed as it relates to the hygiene hypothesis. Environmental risk factors for asthma including allergens, pollutants, infectious factors, and dietary modifications are considered, particularly their potential for primary prevention of asthma. Ongoing cohort studies including the Canadian Allergy and Asthma Prevention Study, the Manchester Allergy and Asthma Study, the Children's Asthma Prevention Study from Australia, and the Prevention and Incidence of Asthma and Mite Allergy Study from the Netherlands are briefly reviewed. A more definitive understanding of genetic background and environmental triggers and their interactions is required before any specific approach to the primary prevention of asthma can be championed aggressively.