Multiple signaling pathways are abnormally activated in non-Hodgkin lymphomas and are considered to play a major role in lymphomagenesis. The events leading to the perturbed oncogenic activity of these pathways are diverse but include several well-defined chromosomal translocations. While some have been exclusively associated with specific NHL subtypes, others may prove to be more global. The targeting agents used to interfere with these pathways for antilymphoma effect are wide ranging and employ different mechanisms of action (see text for details). They can be directed against the molecule of interest specifically or other effectors that are critical in the respective pathway. ASOs indicates antisense oligonucleotides; CDK, cyclin-dependent kinase; PMOs, phosphorodiamidate morpholino ASOs; PNAs, peptide nucleic acids; LNAs, locked nucleic acids; TFOs, triple helix-forming oligonucleotides; siRNAs, short interfering RNAs; DOs, decoy oligonucleotides; IkB, inhibitor of kB; and IKK, IkB kinase.