Interleukin‐10 (IL‐10) is unique among cytokines, as it is considered both as a potent immunostimulatory and immunosuppressive factor. This complex biology has been particularly challenging when trying to define the useful or harmful role of IL‐10 in chronic viral diseases and cancer. In the present review, we emphasize how these multiple roles define IL‐10 as an adaptive molecule, constantly tuning the host response against dangerous and resourceful pathogens.