Systemic sclerosis, or scleroderma, is a rare connective tissue disorder that results in fibrosis and thickening of the skin. The resultant microvascular destruction results in compromised perfusion, leading to Raynaud's phenomenon and, in its most severe state, the formation of non-healing peripheral skin ulcers. This is in addition to a myriad of other systemic fibrotic complications, such as pulmonary arterial hypertension, GI dysmotility, and renal failure. Historically, this has presented a very difficult entity to treat, as the root cause of the disease is unclear and therefore not directly addressed. Pharmacological therapy is focused on the suppression of inflammation and maintenance of microvasculature, to which calcium channel blockers, phosphodiesterase 5 inhibitors and prostacyclin analogues are the mainstay for evidence-based treatment. Other therapies such as statins or endothelin receptor antagonists have been proposed, although more robust evidence is required to determine their efficacy. In more recent years, the value of targeted therapies has also been investigated. Immunosuppressives used in other rheumatological conditions targeting B cells, T cells and cytokine production may have a role in reducing the profibrotic, pro-inflammatory state seen in systemic sclerosis, and therefore modify the disease course rather than simply reducing the extent of tissue damage. If successful, these would help to reduce the incidence of complications in a very morbid disease, for which surgical intervention should be reserved for when no alternative is available.