T helper (Th) lymphocytes, upon activation and differential costimulation, differentiate into various types of Th memory cells with distinct functions. Upon activation in the presence of interleukin-12 (IL-12), Th1 memory cells are imprinted for the expression of interferon-gamma (IFN-gamma), by genetic modification of the ifngamma gene and expression of the transcription factor T-bet. Th1 cells are potent inducers of chronic inflammation of tissues expressing their cognate (auto)antigen. Here, we discuss an anti-inflammatory potential of Th1 cells, based on their expression of IL-10. While the expression of IFN-gamma in memory Th1 cells is independent of the original inducer IL-12, IL-12 is and remains required to induce expression of the regulatory cytokine IL-10 by Th1 memory cells giving IL-12 the potential to act anti-inflammatory during secondary responses.