Psoriasis is a complex inflammatory disorder whose pathogenesis is likely to require the contribution of several genes and environmental triggers. Despite the difficulties posed by the study of multifactorial conditions, significant progress has been achieved in relation to the molecular genetic basis of psoriasis. It has long been recognized that the major histocompatibility complex (MHC) region on chromosome 6p21 harbors the main determinant conferring psoriasis susceptibility. The identification of non-MHC susceptibility regions across the genome has been hindered by the likely occurrence of genetic heterogeneity. Nonetheless, evidence for the assignment of a number of non-MHC loci has been achieved through studies, including the collaborative analysis of large patient cohorts, and also through the observation of overlap between psoriasis and atopic dermatitis susceptibility regions.