Psoriasis is a multifactorial immune skin disease whose etiology involves a strong genetic component, involving several genes encoding proteins involved in epidermal differentiation and immune, inflammatory and pathogen responses, in combination with microbial environmental factors. Although various microorganisms appear to provoke or aggravate the disease, including Staphylococcus aureus, Malassezia and Candida albicans, the association between S. pyogenes throat infections and guttate psoriasis is supported by the strongest clinical evidence. Furthermore, the identification of peptidoglycan-specific T cells in psoriatic skin lesions has led to the proposal that cell wall peptidoglycan may mediate the link between streptococcal infection in the tonsils and the subsequent induction of skin lesions. These findings suggest that psoriasis may be a possible candidate for therapeutic streptococcal vaccination. Current treatments for psoriasis have several limitations including toxicity and an increased risk of infection and malignancy. In contrast, vaccination could potentially induce long-term tolerance without the side effects caused by global immunosuppression. Future research will need to address the identity of the triggering microbial antigen(s); such knowledge could open the way for vaccination as a therapeutic tool for psoriasis.