Glutathione (GSH) is essential for survival of eukaryotic but not in prokaryotic cells. Its functions in nucleated cells are far from being known. In fact GSH plays an important role in cell proliferation. The purpose of the present review is to summarize the relationship between glutathione and the important events that take place in the nucleus during the cell cycle. Most GSH co-localizes with nuclear DNA when cells are proliferating. However, when cells were confluent no differences between nucleus and cytoplasm could be seen. A number of relevant nuclear proteins are strictly dependent on nuclear redox status. For instance, we found that telomerase is regulated by shifts in glutathione redox potential within values similar to those found in vivo, and alterations in telomerase activity are coordinated with changes in critical cell cycle proteins, particularly Id2 and E2F4. More studies are required to establish the role of nuclear glutathione in the epigenetic control of histone function. The information provided in the present review suggests an important role of nuclear glutathione as a key regulator of epigenetic events that may be critical in the regulation of cell proliferation.