Trace elements produce double-edged effects on the lives of animals and particularly of humans. On one hand, these elements represent potentially toxic agents; on the other hand, they are essentially needed to support growth and development and confer protection against disease. Certain trace elements and metals are particularly involved in humoral and cellular immune responses, playing the roles of cofactors for essential enzymes and antioxidant molecules. The amount taken up and the accumulation in human tissues decisively control whether the exerted effects are toxic or beneficial. For these reasons, there is an urgent need to re-consider, harmonize and update current legislative regulations regarding the concentrations of trace elements in food and in drinking water. This review aims to provide information on the interrelation of certain trace elements with risk of autoimmune disease, with a particular focus on type 1 diabetes and multiple sclerosis. In addition, an overview of the current regulations and regulatory gaps is provided in order to highlight the importance of this issue for everyday nutrition and human health.