Molecules of damage-associated molecular patterns (DAMPs) are a class of substances released to intercellular space or peripheral blood by tissues or cells which are stimulated by insults, ischemia or stress. DAMP molecules can be recognized by Toll like receptors, Nod1-like receptors, or Rig-I like receptors and induce autoimmunity or immune tolerance, which play critical roles in various chronic diseases such as arthritis, atherosclerosis, cancer and systemic lupus erythematosus. DAMP molecules include high-mobility group B protein 1, heat shock proteins and S100 proteins etc. The identification of DAMP molecules and clarification of mechanisms of their action will greatly contribute to reveal the pathological mechanisms of chronic diseases and provide a great opportunity to develop the new strategies for the diagnosis, prevention and treatment for these diseases.