Psoriasis is a chronic inflammatory disease triggered by both genetic and environmental factors. Systemic and biologic therapies used to treat moderate-to-severe psoriasis show significant variability in efficacy, are associated with various degrees of toxicity, and, for biologic therapies, are expensive. There is a great need for non-invasive biomarkers to predict treatment outcomes of these therapies and to individualize care for patients with psoriasis. This article reviews currently recognized pharmacogenetic targets related to the treatment of chronic plaque psoriasis, in particular to biologic therapies. The use of pharmacogenetic and pharmacogenomic approaches to genetically profile patients will allow therapies to be targeted more precisely and safely to individual patients, to optimize the treatment of psoriasis, and minimize unnecessary costs. Characterizing patients with psoriasis according to common molecular mechanisms rather than by clinical phenotype may also allow more selective therapeutic agents to be targeted to genetically distinct groups of patients.