Primary Sjögren's syndrome is an autoimmune disease characterized clinically by dryness of the eyes and mouth. The use of different classification criteria for primary Sjögren's syndrome has led to dramatically different estimates of prevalence and incidence. Despite this, several genetic and environmental factors are thought to play a role in the susceptibility to primary Sjögren's syndrome, as is the current conceptual formulation of the pathogenesis of many other autoimmune maladies. Primary Sjögren's syndrome appears a complicated polygenic disorder with many genes interacting with environmental factors. Similar to many other polygenic autoimmune rheumatic diseases, human leukocyte antigen associations have been reported and confirmed. Additionally, other non-human leukocyte antigen candidate genes have been reported to reveal association with primary Sjögren's syndrome, but, in general, these effects are not confirmed. The authors review the human leukocyte antigen and non-human leukocyte antigen genetic associations herewith, knowing that new technologies are providing access to the entire genome for association studies. No doubt a much more comprehensive description of the genetics of this disorder will soon emerge.