Progress in the understanding of disease processes has provided additional therapeutic targets, best exemplified by the increasing role of biologics in the clinical armamentarium. This article provides a focused review of current treatment paradigms and pathophysiology for asthma, atopic dermatitis, urticaria, as well as Cl inhibitor deficiency. It elucidates the populations in which biologics were studied for the aforementioned disease states, emphasizing characteristics to consider when selecting therapy. It is important to correctly estimate patient outcome before starting therapy based on cost analysis. Treatment decisions need to be guided by appropriate patient stratification based on each individual's underlying phenotype.