Psoriatic arthritis is a form of inflammatory arthritis that is frequently associated with psoriasis. Individuals with this disease present with heterogeneous clinical manifestations, making it challenging to diagnose and select optimal treatment strategies. Perhaps, not unsurprisingly, there are currently no molecular diagnostic or prognostic tests to confirm if a patient has the disease or predict how they may respond to therapy. Instead, a range of classification criteria have been developed, and the experience of the treating clinician is heavily relied upon. It is therefore widely accepted that there is a significant and as yet unmet need for effective molecular markers in psoriatic arthritis. Protein mediators drive disease pathogenesis and, therefore, represent logical potential biomarkers. Indeed, significant advances have recently been made by the introduction of multiplexed protein biomarker tests for monitoring disease activity in rheumatoid arthritis. At the same time, recent advances in proteomics have enhanced the capabilities for the detection and discovery of protein biomarkers. These advances offer renewed opportunities for the development of multi-protein biomarker signatures to support clinical decision-making in the diagnosis, prognosis and treatment of psoriatic arthritis. This review summarises the pathogenesis of psoriatic arthritis, highlighting specific areas of unmet clinical need. Furthermore, it seeks to illustrate how the latest developments in proteomic technologies could be used to enhance our understanding of the molecular pathology of psoriatic arthritis and improve clinical outcomes and quality of life for patients.