HLA-B27 has previously been shown to have an association with uveitis, ankylosing spondylitis, reactive arthritis, ulcerative colitis and psoriasis. The authors of this review provide an update of the epidemiology of HLA-B27 associated ocular disorders. There is great variation amongst ethnic populations of the prevalence of HLA-B27. The highest prevalence has been observed in the Pawaia tribe in Papua New Guinea (53%) with the lowest in Japan (<1%). Among Caucasians the prevalence is between 8-10%. HLA-B27 is virtually absent among sub-Saharan Africans, South American Indians and Australian Aborigines. The prevalence of seronegative (rheumatoid factor negative) spondyloarthropathies varies by ethnic group. HLA-B27 is present in >90% of Caucasian patients with ankylosing spondylitis, and in 30-80% of patients with reactive arthritis. Forty to fifty percent of patients with psoriatic arthritis are HLA-B27 positive. The prevalence of the allele in acute anterior uveitis patients is approximately 50%. Despite this high incidence, indiscriminate testing for HLA-B27 is not recommended in all patients with acute anterior uveitis, due to the high population prevalence of B27 in some ethnic groups. Testing is best directed by a careful and thorough patient history and physical exam, and the identification of certain key clinical features should direct testing for HLA-B27. These features include the presence of symptoms, unilateral, sudden onset and limited duration of anterior segment inflammation. A longitudinal study of HLA-B27-positive patients found a median of three attacks in patients followed for more than one year (range: one to 26 attacks), with a median interval of 14 months (range: one to 420 months). Another study found the average frequency of recurrence was 1.1±0.8 per year in patients up to five years from their initial attack and 0.8±0.6 per year in patients five or more years from their first attack, suggesting recurrence may become less frequent with longer duration of disease. The risk for development of acute anterior uveitis correlates with the duration of the underlying spondyloarthropathy. Therefore, a thorough history assessing for features, such as inflammatory back pain, peripheral arthritis, gastrointestinal or urinary tract abnormalities, and dermatologic manifestations can aid in early detection of a spondyloarthropathy and appropriate rheumatologic referral.