The term aggressive B cell lymphoma includes mainly Burkitt lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) [1], the latter being the most common non-Hodgkin lymphoma (NHL), representing around 40% of all NHL cases. New subtypes of DLBCL identified by genetic profiling, with differing characteristics and prognosis, have now been included in the updated World Health Organization (WHO) classification of hematopoietic and lymphoid tumors [2]. The addition of rituximab to CHOP (cyclophosphamide, vincristine, prednisone, and doxorubicin) chemotherapy has led to a dramatic improvement in the outcome of newly diagnosed DLBCL, with a significant increase in the response rate (a complete response [CR] rate of approximately 80%), and in overall survival (OS) [3,4]. However, despite this improvement, a significant proportion of patients (30–40%) still relapse or progress after first-line treatment. The standard strategy for relapsed patients deemed fit for further therapy consists of a salvage regimen followed by high-dose therapy (HDT) and an autologous stem cell transplant (ASCT). The current salvage therapies, as well as the available prognostic models for predicting response in patients with relapsed/refractory DLBCL, will be outlined in this review.