Raynaud's phenomenon affects most patients who have mixed connective tissue disease (MCTD) and frequently represents the initial manifestation of the disease. It is the cutaneous symptom of a systemic vasculopathy that is characterized by intimal fibrosis and blood vessel obliteration that frequently leads to visceral involvement, particularly pulmonary hypertension. An association between Raynaud's phenomenon and the characteristic autoantibody in MCTD, anti-U1-RNP (ribonucleoprotein), is found across the spectrum of rheumatic diseases, including undifferentiated connective tissue disease, scleroderma, and systemic lupus erythematosus. Capillary nailfold examination represents a valuable tool to identify patients who are at risk for MCTD. The goal in the therapy of Raynaud's phenomenon in MCTD is to decrease the frequency of attacks, to prevent digital ulceration, and to limit progressive vascular damage. Therapeutic regimens include the traditional use of calcium channel blockers and novel vascular therapies.