Delineating the genetic background of adult-onset primary open angle glaucoma (OAG) has proven to be a difficult task. While many OAG loci have been mapped, confirmation of the disease-associated gene within each region has been a stumbling block.  Myocilin was the first identified OAG gene.  One particular variant in this gene, the Thr377Met mutation, has given glimpses of the complexity of the OAG story. Most of the families carrying the Thr377Met change have a relatively large number of individuals with glaucoma; however, not everyone with the disease has the myocilin mutation.  Moreover, a large Greek family in which OAG was mapped to the GLC1C locus on chromosome 3 was later shown to also have the Thr377Met MYOC variant segregating through the family. Haplotype analysis of nine families around the world carrying the Thr377Met MYOC SNP suggests that this variant has arisen at least twice and is most common in individuals with Balkan ancestry. The highest concentration of this variant is found in a small village in the Greek Pindos mountain range. Potentially, the Thr377Met SNP may be used in variable component analysis to help tease out the other OAG genes in this specific population. While much work remains to be done in identifying OAG susceptibility genes, the Human Genome Project, HapMap and sophisticated genetic analyses, such as SOAR, make this immense project feasible.