Autoimmune diseases can be preceded by a symptom-free phase which is defined by the presence of autoantibodies, and may last for many years. These autoantibodies may have a high positive predictive value for disease onset, severity and organ-specific complications, especially in genetically prone individuals. Characteristic autoantibodies and susceptible genes have been identified in many autoimmune systemic and mucocutaneous diseases such as systemic lupus erythematosus, pemphigus, vitiligo, dermatitis hepretiformis and even psoriasis. Prevention of overt disease may be achieved once high-risk individuals are identified and triggering factors are avoided. Numerous environmental factors, such as vitamin D deficiency, ultraviolet light, smoking, drugs, etc., that may trigger autoimmunity have been found. Alternatively, even if the autoimmune disease cannot be prevented, it may be postponed or attenuated. Thus, although large body of evidence has accumulated on characteristic autoantibodies, susceptible genes and environmental factors, many more large scale studies are needed to assess their predictive value, the preventive measurements and the means to apply them to clinical management of healthy population and high-risk individuals.