Diffuse Large B-Cell non-Hodgkin’s Lymphoma (DLBCL) is an aggressive form of non-Hodgkin’s Lymphoma (NHL). During the past 30 years the treatment of DLBCL has evolved to a point where the disease is curable in many patients. The introduction of Positron Emission Tomography (PET) has made a critical contribution to the accurate definition of clinical stage at presentation and the accurate assessment of disease clearance at the end of treatment. More recently early interim PET has been shown to be a good indicator of potential for cure. Gene expression profiling (GEP) of DLBCL has been demonstrated to identify disease subsets with both biological and clinical significance and to provide an independent predictor of response to treatment.