Systemic sclerosis (SSc) is a connective tissue disorder characterized by the fibrosis in the skin and internal organs. SSc is characterized by the presence of autoantibodies that are produced by B lymphocytes. Recently, the importance of B lymphocytes in immune response and autoimmunity has been recognized. CD19, which is a critical cell-surface signal transduction molecule of B cells, positively regulates signaling through B cell antigen receptor and controls autoantibody production. B cells from SSc patients exhibit CD19 overexpression that results in disturbed peripheral B cell homeostasis characterized by increased naive B cells and decreased but activated memory B cells. These findings indicate that B cells are potential therapeutic targets in SSc. Since SSc is a heterogeneous disorder, the subset classification of limited cutaneous SSc and diffuse cutaneous SSc (dSSc) is critical for predicting prognosis and selecting appropriate treatment. Although none of drugs have been proved to be effective for SSc by controlled studies, there are some therapeutic choices that may be effective for patients with early dSSc. Oral low-dose steroid is frequently effective for skin sclerosis, when it is used for early dSSc patients with edematous and rapidly progressing skin fibrosis. Many uncontrolled trials have shown that treatment with cyclophosphamide plus steroid may be effective for SSc patients with active alveolitis. Since it is difficult to remove fibrosis once established in SSc, it should be emphasized that early diagnosis and early treatment of dSSc are critical for management of SSc.