Psoriasis (Ps) is a common immune-mediated disease characterized by red, scaly patches with painful phenotypes. The distribution of Ps is approximately 0.2–2% worldwide and is driven by the interactions between inherited susceptibility alleles and environmental triggers. So far, the strongest Ps susceptibility locus identified is PSORS1 (Ps susceptibility locus 1), located within the major histocompatibility complex (MHC). Other genes, such as IL12B, IL23R, IL23A, TNFAIP3, IL13 etc., are also strong contributors for this complex disease. Ps is associated with the DCs and T cells, in which inflammatory myeloid dendritic cells release IL-23 and IL-12 to activate Th17, Th1 and Th22 cells to produce abundant Ps-associated cytokines such as IL-17, IFN-γ, TNF-α, and IL-22. These cytokines affect keratinocyte responses to amplify Ps inflammation. Ps can be provoked or exacerbated by specific microbial pathogens such as bacteria (S. aureus and, Streptococcus pyogenes), viruses (human papillomavirus and endogenous retroviruses), and fungi (Malassezia and Candida albicans). A recent research suggests that the skin microbiome in patients with Ps is distinct from that of healthy controls. Moreover, the gut microbiome and enterotype also showed for the first time a specific “psoriatic core intestinal microbiome” that clearly differs from the one present in healthy population. The treatment options for Ps symptoms fall into three major categories: Topical (vitamin D analogues, corticosteroids, retinoids, dithranol and coal-tar products), phototherapy [UVB, UVB + psoralen, UVA, UVA + psoralen (PUVA)] and systemic treatments (biologics alone or in combination with methotrexate or cyclosporin). Thus, understanding disease causative factors and mechanisms are important for developing future therapeutics and for optimal disease management. © 2004 - 2023 Nova Science Publishers