Autoimmune diseases are classic examples of multifactorial disorders in which a large number of genes interact with environmental factors to form the final phenotype. Identification of the genes involved in these diseases is a daunting challenge. Initially the search involved the candidate approach where polymorphisms in suspected genes were tested for association in large cohorts of patients and controls. Today, the most widely used method is genome-wide association studies (GWAS), a method based on screening large panels of patients and controls with hundreds of thousands of single nucleotide polymorphisms (SNPs), with microarray-based technology. Unique families in which autoimmune diseases are caused by single genes are another alternative. The identification of candidate genes is often followed by studies that provide biologic plausibility for the findings. The widely expanding list of genes involved in autoimmune conditions show that the same genes frequently underlie the pathogenesis of different autoimmune diseases. Despite all available resources, the main void of heritability in autoimmune conditions is yet to be discovered. Identification of these genes will help define new biological pathways and identify novel targets for the development of new therapeutic drugs.