Allergic diseases, such as asthma, are the result of complex gene-environment interactions. The focus for prevention of allergic disease has been on environmental control. Environmental exposures begin during the intrauterine period, during which a T-helper-2 immune phenotype is promoted. Food allergy frequently occurs during the first year of life, and avoidance of exposure must begin in early pregnancy and must be complete to be effective. Partial avoidance strategies have not been successful. Current data do not allow us to specifically recommend breastfeeding for the prevention of allergy and allergic diseases, but for other important reasons, breastfeeding (particularly exclusive breastfeeding) should be encouraged for at least the first 4 mo of life. Sensitization to allergens is one of the strongest determinants for subsequent development of asthma. There is a strong relationship between exposure to house dust mites, allergen sensitization, and asthma. However, exposure to pets and animals in a farming environment early in life may actually be protective for the development of allergy and asthma. Specific recommendations relating to these exposures requires additional research, but genetics clearly plays an important role in that process. To date, only a multifaceted intervention program has been successful as a primary prevention strategy for the development of asthma in young children. The specific components of the multifaceted intervention and the duration of protection have not yet been defined. It is increasingly clear that gene-directed environmental manipulation undertaken in a multifaceted manner during a "window of opportunity" is critical in the primary prevention of allergy and allergic diseases like asthma.