Since the discovery of the first histone lysine demethylase in 2004, two protein families with numerous members have been identified that demethylate various histone lysine residues. Initial studies of the histone lysine demethylases focused on their in vitro enzymatic activity but, more recently,model organisms have been used to examine the roles of these enzymes in vivo. Here, we review recent insights into the roles of the histone lysine demethylases in multiple aspects of development across various species,including in germline maintenance and meiosis, in early embryonic development and differentiation, and in hormone receptor-mediated transcriptional regulation.