Adaptive immune responses are supported the random generation of immunoglobulin and T cell receptors to make repertoires that cover the entire spectrum of potential foreign antigens. due to the random nature of the immune adaptive receptors and their extensive diversity, an outsized fraction of the antibodies and T cell receptors that are generated a day by our B and T cells are reactive to self-components. If we increase this self-reactive capacity the notion that the system harbors a fantastic ability to cause tissue damage and destruction, we will forever marvel how it's that the majority folks don't develop autoimmunity during our life. In fact, a permanent battle for balance takes place in our body to make sure that the system is active and effective against dangerous foreign and self (i.e., cancer-related) proteins, while it remains non reactive against us. Maintaining this balance isn't, indeed, a simple task because the battle is lost leading to overt autoimmunity in approximately 3% of the human population. The onset of autoimmunity may be a dynamic, multi-factorial process that needs the breaching of multiple checkpoints. Immune regulation is effected via regulatory cells and via regulatory membrane and soluble molecules which will be potentially manipulated to stop autoimmunity and achieve tolerance. Manipulating the system for therapeutic purposes may be a difficult but important goal, and up to date findings propose a spread of novel targets for clinical intervention that are just beginning to be explored.