Enterovirus D68 (EV-D68) has gained attention as a respiratory and neuropathogen, particularly affecting children and causing outbreaks of severe respiratory illness and acute flaccid myelitis. This review explores the current state of knowledge regarding the immunology of EV-D68, delving into the intricate interactions between the virus and the host immune system. From the initial encounter of the virus with the innate immune response to the development of adaptive immunity, we navigate through key aspects of EV-D68 immunology. 1. Innate Immune Response: The journey begins with the recognition of EV-D68 by the innate immune system. Pattern recognition receptors (PRRs) identify viral components, triggering a cascade of antiviral responses. The role of interferons, natural killer cells, and other innate immune effectors in controlling early viral replication is highlighted. 2. Adaptive Immunity: The adaptive immune system orchestrates a more targeted and specific defense against EV-D68. B cells produce antibodies that recognize and neutralize the virus, while T cells play a crucial role in coordinating and regulating the immune response. This section explores the dynamics of antibody-mediated immunity and the cellular immune response in the context of EV-D68 infection. 3. Viral Evasion Mechanisms: EV-D68 employs various strategies to evade the host immune response, including antigenic variation and interference with host antiviral pathways. Understanding these mechanisms is vital for developing effective countermeasures. 4. Vaccine and Therapeutic Developments: A critical aspect of EV-D68 immunology is the ongoing efforts to develop vaccines and antiviral therapies. This section provides an overview of current research and potential strategies for preventing and treating EV-D68 infections. 5. Future Perspectives: The review concludes by highlighting the gaps in our understanding of EV-D68 immunology and proposing avenues for future research. The importance of a comprehensive approach to tackle this evolving respiratory pathogen is emphasized.