Cover: Traditional scheme for allergen-driven events that present anti-asthma drug targets. The scheme begins with initial (1°) allergen processing by dendritic cells and then MHC Class II restricted antigen presentation to T helper type 0 (Th0) cells that differentiate into Th2 cells. Under other conditions, Th0 cells may differentiate to Th1 cells or regulatory (Tr) cells. Under these conditions, Th2 cells then provide help for B cell production of IgE Ab. Subsequent (2°) allergen exposure may activate mast cells (via IgE-dependent Fcε RI cross-linking) and Th2 cells (via MHC-dependent presentation to TCR and co-stimulation). These events then lead to activation of eosinophils. Each of these effector immune cell types release a variety of cytokines, eicosanoids, proteases, and other products that act on airway parenchymal cells (epithelial cells, myofibroblasts, and smooth muscle cells) to cause airway remodeling, hypersecretion, and hyperreactivity. Four general areas for therapeutic intervention (in boxes labeled 1-4) include: (1) allergen sensitization and IgE production, e.g., by allergen desensitization; (2) immune cell activation, e.g., by inhibition of specific cell surface receptors or downstream signaling events; (3) generation and/or production of immune cell products, e.g., by selective antagonists; and (4) altered parenchymal cell behavior, e.g., by modifying cell surface receptors, signaling, or gene expression. For more information see Translational Review by Holtzman beginning on page 163.