Chronic lymphocytic leukemia (CLL) is a very heterogeneous disease with significant variation in clinical presentation, time to disease progression, survival, and aggressiveness of clinical course. A subgroup of patients who have been repeatedly identified as having a poor response to therapy are those with del(17p13.1)--identified by either interphase cytogenetics or other comparable strategies. Although there has been much progress over the past few years in the development of new therapeutic targets for CLL patients, this subgroup has continued to lag behind others. Because of the poor response or significant therapy-related toxicity experienced by patients with del(17p13.1)--and the small number of these patients included in clinical trials--current guidelines are unable to provide suggestions for the care of newly diagnosed, symptomatic but untreated patients (as well as relapsed patients) in this subgroup on account of the modest amount of evidence. However, novel agents are on the horizon that appear to be significantly more effective in this patient population, and these will likely shape the standard of care for these patients in the future.