Intravenous fludarabine is a well-established therapy for the first-line treatment of chronic lymphocytic leukemia and the standard of care for second-line treatment. More recently, an oral formulation of fludarabine has been developed, with equivalent efficacy and tolerability to the intravenous formulation, but with improved convenience of administration and potentially greater cost effectiveness. In previously treated patients receiving oral fludarabine monotherapy, overall response rates of 46-51% were achieved, depending on the response criteria used. Oral fludarabine is also an effective first-line treatment, both as monotherapy (overall response 72-80%) and in combination with cyclophosphamide (overall response 80%). Infusion-related adverse effects are eliminated with oral administration. Importantly, WHO performance status is maintained or improved in more than 50% of patients. As oral fludarabine can be taken at home, administration costs are greatly reduced due to fewer physician and nursing interventions and less time spent in hospital. Oral fludarabine was approved first in the UK as second-line therapy for chronic lymphocytic leukemia and, based on its ease of administration and potentially greater cost effectiveness, is recommended in preference to the intravenous formulation by the UK National Institute for Clinical Excellence. The oral formulation is also now available in the majority of European countries. Therefore, with equivalent efficacy and tolerability to the intravenous preparation, oral fludarabine gives the hematologist an important new option in the management of chronic lymphocytic leukemia.