AbstractHistone lysine demethylases (KDMs) are enzymes that remove the methylation marks on lysines in nucleosomes' histone tails. These changes in methylation marks regulate gene transcription during both development and malignant transformation. Depending on which lysine residue is targeted, the effect of a given KDM on gene transcription can be either activating or repressing, and KDMs can regulate the expression of both oncogenes and tumour suppressors. Thus, the functions of KDMs can be regarded as both oncogenic and tumour suppressive, contingent on cell context and the enzyme isoform. Finally, KDMs also demethylate nonhistone proteins and have a variety of demethylase‐independent functions. These epigenetic and other mechanisms that KDMs control make them important regulators of malignant tumours. Here, we present an overview of eight KDM subfamilies, their most‐studied lysine targets and selected recent data on their roles in cancer stem cells, tumour aggressiveness and drug tolerance.