The many rheumatologic manifestations associated with chronic hepatitis C virus (HCV) infection include arthralgia, myalgia, arthritis, vasculitis, and sicca syndrome. Arthralgia is the most common extrahepatic manifestation and may indicate mixed cryoglobulinemia or an adverse reaction to interferon therapy. HCV arthritis unrelated to cryoglobulinemia is far less common but constitutes an independent entity. The picture may mimic rheumatoid arthritis (RA), particularly as rheumatoid factor is present in 50-80% of cases. Tests are usually negative for antibodies to cyclic citrullinated peptides (anti-CCP), which may help to differentiate the two conditions. The management of HCV arthritis is empirical and poorly standardized. Although low-dose glucocorticoid therapy, hydroxychloroquine, and methotrexate have been used successfully in several patients, little is known about their hepatic safety profile. Arthritis associated with cryoglobulinemia usually responds to antiviral treatment. Sicca syndrome is common in patients with chronic HCV infection and shares similarities with primary Sjögren syndrome, suggesting that HCV infection may deserve to be included among the causes of secondary Sjögren syndrome. HCV-associated vasculitis is usually related to cryoglobulinemia, although a few cases of polyarteritis nodosa-like disease affecting the medium-sized vessels have been reported. Other conditions reported in patients with chronic HCV infection include fibromyalgia, systemic lupus erythematosus (SLE), antiphospholipid syndrome, and osteosclerosis.