The clinical course of chronic lymphocytic leukemia (CLL) shows a marked heterogeneity, with a median survival ranging from 2 to 20 years at different disease stages. This unpredictable course has inspired clinical hematologists and oncologists to search for parameters which predict survival and disease progression. This effort resulted in different staging systems, two of which, the Rai and Binet staging systems, have become most popular because of their simplicity. They identify three major groups of patients with different survival. Since patients at early stages have a relatively good prognosis, only advanced stages used to be treated by chemotherapy with alkylating agents. With the advent of potentially curative, but more aggressive treatment options for CLL, additional prognostic criteria are required to predict the outcome more precisely, in particular in young patients with early disease. It is the intent of this review to summarize the current knowledge on both established and new prognostic factors in CLL, some of which might help to define risk-adapted treatment protocols in the near future.