Scleroderma is a complex, multisystem autoimmune rheumatic disease with wide heterogeneity in phenotype and outcome. There are often coexisting ongoing pathologic processes including immune system activation, progressive fibrosis, and vascular disease in subsets of patients. Currently, it is challenging to identify patients at risk for developing adverse outcomes and to determine which patients are responding to current therapies. For these reasons, it is highly valuable to find easily measurable biomarkers that may represent ongoing disease activity or treatment response. This review examines the current state of biomarker development in systemic sclerosis and identifies areas in which further work should be directed.