Scleroderma (systemic sclerosis [SSc]) is a rare progressive autoimmune disease characterized by skin fibrosis and varying degrees of vasculopathy manifesting as Raynaud’s disease and, often, painful digital ulcers. Risks of pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and renal crisis are higher in SSc patients than in the general population and underlie a high mortality rate. Systemic small-molecule immunomodulators are prescribed for ILD and skin fibrosis, while PAH and vasculopathy are treated with varying combinations of calcium-channel blockers, endothelin receptor antagonists, PDE-5 inhibitors, and prostacyclin analogues. Renal crisis is treated acutely with ACE inhibitors, which are credited with having tremendously reduced mortality from this complication. Still, current treatments are only marginally effective, underscoring a tremendous need for genuinely effective disease-modifying therapies and antifibrotics to treat scleroderma (systemic sclerosis).