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Purpose of Review: Racial disparities appear to exist in the susceptibility and severity of systemic sclerosis (SSc, scleroderma) and are responsible for a greater health burden in blacks as compared with whites. Disparities in socioeconomic status and access to healthcare do not sufficiently explain the observed differences in prevalence and mortality. It is important to determine whether there might be a biologic basis for the racial disparities observed in SSc., Recent Findings: We present data to suggest that the increased susceptibility and severity of SSc in blacks may result in part from an imbalance of profibrotic and antifibrotic factors. Racial differences in the expression of transforming growth factor-β1 (TGF-β1) and caveolin-1, as well as differences in the expression of hepatocyte growth factor and PPAR-γ, have been demonstrated in blacks with SSc, as well as in normal black individuals. A genetic predisposition to fibrosis may account for much of the racial disparities between black and white patients with SSc., Summary: A better understanding of the biologic basis for the racial disparities observed in SSc may lead to improved therapies, along with the recognition that different therapies may need to be adapted for different groups of patients.