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Chemiluminescence has traditionally been used to study the nature of the oxidative bactericidal mechanisms of neutrophils and monocytes, intrinsic defects of abnormally functioning neutrophils or monocytes and cell activation. During the last ten years, Chemiluminescence has been applied in a wide variety of techniques, including immunoassays, protein blotting and toxicological and pharmacological tests (e.g. after exposure to antibiotic or immunomodulators agents, such as adjuvants and cytotoxic drugs). In this review, we discuss some promising clinical applications of Chemiluminescence in clinical immunology for the study of autoimmune diseases, inflammatory responses, endocrine disorders, immunodeficient states, mucosal immune responses against drugs and pathogens and host responses against tumors and infections. Further, we review the numerous advantages of Chemiluminescence-based methods over other methods to assay the same endpoints, which facilitate their use in the current practice of clinical immunology.