Immunoglobulin E (IgE) and mast cells are crucial in the pathophysiology of allergic diseases, including anaphylaxis and acute allergic reactions. However, recent evidence suggests that they also play significant roles in the long-term changes and tissue remodeling associated with chronic allergic inflammation in conditions like asthma. This review discusses the complex interplay between IgE and mast cells, highlighting their both interdependent and independent roles in the development of allergic disorders. IgE can regulate mast-cell functions and influence mast-cell activation through mechanisms independent of mast cells. Mast cells can also contribute to allergic responses without direct interaction with IgE. The review explores the mechanisms by which IgE and mast cells amplify allergic responses, including the role of CD23 and FcεRI. It also examines the potential therapeutic approaches targeting IgE or mast cells to manage allergic diseases, such as the use of omalizumab and blocking peptides. The complexity of allergic disorders and the redundancy in effector mechanisms are discussed, emphasizing the need for a comprehensive understanding to develop effective treatments.Immunoglobulin E (IgE) and mast cells are crucial in the pathophysiology of allergic diseases, including anaphylaxis and acute allergic reactions. However, recent evidence suggests that they also play significant roles in the long-term changes and tissue remodeling associated with chronic allergic inflammation in conditions like asthma. This review discusses the complex interplay between IgE and mast cells, highlighting their both interdependent and independent roles in the development of allergic disorders. IgE can regulate mast-cell functions and influence mast-cell activation through mechanisms independent of mast cells. Mast cells can also contribute to allergic responses without direct interaction with IgE. The review explores the mechanisms by which IgE and mast cells amplify allergic responses, including the role of CD23 and FcεRI. It also examines the potential therapeutic approaches targeting IgE or mast cells to manage allergic diseases, such as the use of omalizumab and blocking peptides. The complexity of allergic disorders and the redundancy in effector mechanisms are discussed, emphasizing the need for a comprehensive understanding to develop effective treatments.