Type 1 diabetes (T1D) is a chronic T-cell mediated autoimmune disease characterized by destruction of beta cells. Although new data have better defined the complex etiology underling the interrelation of genetic and environmental factors in the natural history of T1D, relevant pieces of the puzzle still are missing. Genetic predisposition is mainly associated to some histocompatibility leukocyte antigen (HLA) alleles; however, recent data suggest that new as well as still unknown genes might better define the complex multigenetic risk of the disease. In addition to the genetic effects, the concordance in familial aggregation in T1D indicates a pivotal role of environmental factors in the course of the disease, facilitating autoantibodies production. JDRF has recently proposed a new early stage of T1D according to which the detection of two or more autoantibodies in the blood, might describe those children at increased risk of developing T1D during the following years. In contrast to the improvements reached by prediction models, to date primary, secondary and tertiary prevention have still failed to achieve a safe and efficacious intervention strategies. Anyway, the most recent progresses in this field pave the way for future studies, with the aim of preventing T1D in children.