Immune mediated inflammation that culminates in severe tissue necrosis is the hallmark of diseases that result from an inappropriate response to antigen. The inflammatory response becomes chronic when antigen is non-limiting and persists until the reactive tissue is destroyed, or the environment is changed and exposure to antigen is eliminated. The purpose of this review is to: (1) briefly outline common features of immune related inflammatory diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), inflammatory bowel disease (IBD), and allergic asthma; (2) provide a rationale for the development of gene based drugs for these indications; and (3) describe current experimental results that support the usefulness of this approach for creating novel DNA based therapeutics.