This chapter contains sections titled: Introduction Questions Literature‐search strategy and inclusions When should therapy be initiated? What is the best initial treatment for symptomatic patients? What treatment options exist for a patient who has relapsed after initial therapy with fludarabine? What are the indications for plasmapheresis? References Introduction Questions Literature‐search strategy and inclusions When should therapy be initiated? What is the best initial treatment for symptomatic patients? What treatment options exist for a patient who has relapsed after initial therapy with fludarabine? What are the indications for plasmapheresis? References