Asthma is a complex multigenic disease. The most frequently encountered form is atopic asthma, which is at its highest prevalence during childhood/young adulthood, and this represents the main focus of this review. The primary risk factor for atopic asthma is sensitization to perennial aeroallergens resulting from a failure to generate protective immunologic tolerance. This tolerance process is orchestrated by airway mucosal dendritic cells and normally results in programming of regulatory T cells, which inhibit activation of the T_H2 memory cells that, among other activities, drive IgE production and prime the effector populations responsible for IgE-mediated tissue damage. Emerging evidence highlights the complexity of this process, in particular the iterative nature of the underlying interactions between innate and adaptive immune mechanisms in which virtually every signal emanating from one cellular compartment provokes an answering response from the other. To further complicate this picture, the local mesenchyme can also interpose signals to fine tune immune responses to optimally meet local microenvironmental needs. Perturbation of the balance between these interlinked innate and adaptive immune pathways is increasingly believed to be the basis for disease expression, and in the specific case of atopic asthma, the prototypic example of this (discussed below) is acute exacerbations triggered by viral infections.