Psoriasis is an immune-mediated inflammatory disease (IMID) characterized by skin inflammation, epidermal hyperplasia, increased risk of arthritis, and cardiovascular morbidity. Substantial evidence indicates that psoriasis is driven by abnormal interactions between cells of the innate and adaptive host defence systems, including keratinocytes, dendritic cells, and T-cells, resulting in a dysregulated immune response and markedly increased epidermal proliferation. The precise aetiology of psoriasis remains unknown. Here, we review how innate and adaptive host defence responses are regulated by genetic factors that modulate the overall risk of psoriasis and dictate whether the disease affects the skin and/or the joints. Specifically, we review the epidemiologic basis for considering psoriasis as a genodermatosis, summarize knowledge derived from linkage and association studies of cutaneous psoriasis (PsC) and psoriatic arthritis (PsA), and attempt to relate genetic and immunologic discoveries in a pathogenetic framework that may eventually allow prediction of the development of PsA in psoriatic individuals.