TNF inhibitors and anti-p40IL12/23 monoclonal antibodies are efficacious treatments for moderate-to-severe psoriasis. However, the formation of anti-drug antibodies (ADA) with biologics may prevent patients from achieving a full clinical response. ADA have been reported in patients treated with etanercept, infliximab, adalimumab or ustekinumab at rates of 0–18.3%, 5.4–43.6%, 8.8–44.8% and 3.8–5.4%, respectively. Antibodies against etanercept have no apparent effects on clinical response, whereas antibodies against infliximab or adalimumab have been associated with diminished clinical response. The significance of ADA against ustekinumab is yet to be determined. Data regarding management strategies to counteract ADA formation and their effects are limited in psoriasis patients. However, some evidence suggests that concomitant immunomodulators such as methotrexate may suppress ADA development in psoriasis. ADA specific to one biologic do not appear to carry cross-linking potential with other biologic agents. ADA formation needs to be considered as a possible factor contributing to diminished response from biologic agents.