Transformation of chronic lymphocytic leukemia (CLL) to aggressive lymphoma is known as Richter syndrome (RS). In the CLL population considered as a whole, the prevalence of RS development ranges from 2 to 7 %. The most common pathologic phenotype at the time of RS transformation is diffuse large B-cell lymphoma (DLBCL), while, in a small fraction of cases, the transformed phase shows pathologic features mimicking Hodgkin lymphoma. TP53 disruption and MYC activation cooperate as dual hits in driving DLBCL transformation. Two biomarkers (NOTCH1 mutations and usage of the immunoglobulin VH CDR3 subset 8) may help in identifying CLL patients at risk of DLBCL transformation to be considered for close monitoring and a careful biopsy policy. In the presence of clinical features suspicious of RS, diagnosis of transformation and choice of the site of biopsy may take advantage of (18)FDG PET/CT. The prognosis of RS transformation is generally highly unfavorable. However, the pattern of survival is not homogeneous and may be predicted on clinical and biological grounds. RS that are clonally unrelated to the paired CLL phase are biologically and clinically different from clonally related cases, and should be considered, and probably managed, as a de novo DLBCL arising in the context of CLL. Rituximab-containing polychemotherapy represents the backbone for induction treatment in patients with clonally related DLBCL transformation. Younger patients who respond to induction therapy should be offered stem cell transplant to prolong survival.