Although the outcome of patients with non-Hodgkin lymphoma (NHL) has, in general, improved signifi cantly over years, treatment failure due to drug resistance remains a problem. Recently, the focus of drug development has shifted from conventional cytotoxic drugs to agents directed against specifi c molecular targets and immunotherapy. Th is has mainly been driven by advances in the understanding of the molecular pathogenesis of NHL. A large number of promising new agents are in preclinical and clinical development. Th e challenge for clinicians is how best to incorporate them into already existing treatment regimes. Th is review will highlight some recent clinical trials focussing on targeted small molecules and monoclonal antibodies in NHL.