B-cell disorders include a large group of malignant and nonmalignant diseases with tremendous variation in incidence, natural history, treatment, and prognosis. This article will focus on adult idiopathic thrombocytopenic purpura (ITP) and chronic lymphocytic leukemia (CLL). Clinicians must individualize treatment for ITP and CLL to each patient. Observation without intervention is appropriate for some patients, whereas immediate treatment is indicated for others. Deciding when to treat and which agents to use can be difficult, but new therapeutic options are emerging for both conditions.