Anti-drug antibodies (ADAs) may develop against originator biologic and biosimilar therapies used for the treatment of psoriasis and may be the cause of initial therapeutic non-response or diminished therapeutic response over time. Comparing immunogenicity between therapeutic agents is challenging owing to the variation in assays used for detection, among other reasons. Using the results of a PubMed search for psoriasis clinical trials disclosing the rates of ADAs for originator biologic and biosimilar therapies approved for the treatment of psoriasis within the last 5 years, this review discusses the rates and potential clinical impact of ADA formation in patients with psoriasis managed with originator biologic and biosimilar therapies, along with novel methods of ADA testing. Anti-drug antibodies are detectable in all biologic and biosimilar therapies approved for the treatment of psoriasis in the last 5 years, and the effect of ADAs on clinical response varies by agent. Novel immunoassays used for the detection of ADAs may have increased sensitivity compared with traditional assays, although the increased rate of detection may not correlate with decreased clinical response and the decision to test for the presence of ADAs may vary from patient to patient. Though ADA formation seems ubiquitous with the use of biologic agents for the treatment of psoriasis, the increased rates of ADAs detected by novel immunoassays may not necessarily correlate with decreased treatment efficacy.