The knowledge about biological mechanisms contributing to lymphomagenesis represents the basis for targeted therapies in lymphoproliferative disorders. Herein, we provide a short overview about the novel drugs targeting B-cell non-Hodgkin lymphomas, with a focus on diffuse large B-cell lymphomas. Due to the plethora of new drugs, we present some of the most important new drug developments in lymphoma treatment, namely humanized monoclonal antibodies, monoclonal antibody conjugates, immunomodulatory agents, and tyrosine kinase inhibitors. The use of these agents alone or in combination with chemotherapy showed promising results with a good safety profile in a setting of relapsed/refractory lymphomas. Since many of them demonstrated to be highly active, several clinical trials evaluating their efficacy in first-line treatment are ongoing.