Objective: This article reinforces the reader's knowledge of the multifactorial nature of allergic diseases and of the heterogeneity of allergic phenotypes. Data Sources: Personal studies and an evidence-based approach is used to support the assumption that three major abnormalities concur in the pathophysiology of allergic diseases: 1) enhanced allergen recognition and specific immune response; 2) a T helper 2 cytokine profile that results in polyclonal immunoglobulin E activation and mast cell-eosinophilic inflammation; and 3) organ hyperreactivity. Study Selection: Examples of genetic and environmental factors that preferentially influence each of these distinct pathophysiologic abnormalities are provided. Results: Data presented indicate that allergic diseases distribute along a wide spectrum depending on the preferential pathophysiologic abnormalities operating in the individual patient. Conclusions: Categorization of allergic patients into distinct clinical phenotypes might result in a more patient-oriented (rather than disease-oriented) approach, and hence, better management.