Endotherapia is a new therapeutic approach against chronic diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and rheumatoid arthritis. It combines the evaluation of circulating antibodies directed against specific self-antigens and self-antigens modified by free radicals. Here, we review the literature concerning this topic. In addition, our biological assays have allowed us to follow up the evolution of chronic diseases along time, checking remission phases. For more than 25 years, our scientific group has suggested that the chronicity of diseases may be due to nonpathological bacteria living in different biotopes. Endotherapia is the result of immunopathologic work addressing chronic incurable diseases with a multifactorial etiology. Several genes are susceptible to toxic environmental immunologic agents. Thus, the intestinal ecosystem plays an important role in these mechanisms. Therapy is a "tailor-made" combination (MG1/RA, GEMSP) of the small molecules (e.g., vitamins...) linked to poly-L-lysine (PLL). Each individual linkage to PLL offers great advantages owing to the chemical characteristics of PLL (e.g., non-immunogenic), increasing the half-life of the active PLL derivatives. Clinical trials have enabled us to confirm very good safety. Our results confirm the efficacy of the approach and we believe that it could be very promising for chronic diseases.