Hodgkin's lymphoma (HL) is characterized by a minority of neoplastic cells, the so‐called Reed–Sternberg (RS) cells, and an admixture of reactive cells including lymphocytes, plasma cells, eosinophils and histiocytes. Cytokines produced in HL, either by RS or infiltrating cells, might explain the presence and maintenance of an impaired immune response. Chemokines (cytokines with chemoattractant properties) produced by RS cells play a major role in leukocyte trafficking. These molecules with specific receptor affinities contribute, for example by attracting TH2‐like T cells, to the maintenance of a favorable environment for survival of RS cells.

Cross‐talk between RS cells and reactive elements involves several cytokine/chemokines that process proliferative [interleukin (IL)‐13 and IL‐17], immunosuppressive (IL‐10 and transforming growth factor‐β) and background formation (IL‐5, TARC, MDC, IP‐10, RANTES, Mig and others) messages. These autocrine and paracrine interactions lead to an environment where RS cells are able to proliferate, escape from apoptosis and survive host anti‐tumor defense.

The proper modulation of these complex pathways may allow the development of new strategies in HL therapy.