Psoriatic arthritis (PsA) is a systemic inflammatory disease characterized by musculoskeletal involvement mostly associated with skin psoriasis. PsA is associated with significant morbidity and disability, and thus constitutes a major socioeconomic burden. For therapeutic strategies, early diagnosis and sufficient treatment lead to the best outcome with prevention of structural damage and loss of function. The combination of biologics (e.g., tumor necrosis factor inhibitors) and methotrexate (MTX) shows a significantly stronger clinical effect in the treatment of rheumatoid arthritis compared to biologic monotherapy as demonstrated by randomized controlled clinical trials. However, the influence of concomitant MTX on biologic therapy for PsA has not yet been fully clarified due to the lack of data from controlled studies that directly compare both treatment strategies, biologic monotherapy and combination of biologic and MTX. Moreover, data from subgroup analyses, register studies and from non-interventional clinical trials show discrepant results. The Germany-wide MUST study is a placebo-controlled, multicenter, randomized study to investigate the influence of MTX on the efficacy, safety and adherence to biologic therapy with ustekinumab in patients with active PsA. The aim of the study is to evaluate whether MTX naive patients would achieve a greater disease improvement with the combination of MTX and biological therapy than with a biologic monotherapy and whether MTX patients who, in addition to MTX, start a biologic therapy would become worse if MTX is discontinued. Data from randomized and controlled clinical trials are important to better understand the role of MTX as a concomitant medication in patients with PsA. The MUST study offers the ideal opportunity to investigate this question in a controlled study and to find out whether the addition of MTX to ustekinumab therapy is beneficial for patients. The results of this and other studies could improve PsA treatment by potentially omitting additional, possibly ineffective, medication that might increase the risk of adverse reactions. This article gives an overview of the current knowledge and published data regarding the effect of MTX as additional therapy to biological treatments in PsA patients. Additionally, the article introduces current efforts to evaluate the role of MTX for PsA treatment, including the MUST study.