Alcohol exposure affects gene expression in the brain and can lead to addiction in humans and other organisms. Epigenetic changes act on DNA or Histones to alter the transcription, or expression, of genes. Histone modifications include both acetylation and methylation; the latter was considered stable until the discovery of histone demethylases (KDM). Histone methylation/demethylation can promote or silence transcription. The majority of KDMs belong to a group of enzymes that contain a jumonji C (JmjC) domain; these JmjC demethylases regulate several physiological processes. The fact that alcohol and KDMs produce long lasting transcriptional changes suggests JmjC demethylases have a role in alcohol consumption and development of addition. In this study, we assess behavioral changes related to JmjC mutations in Drosophila melanogaster. We measured resistance to sedation (ST50 on an initial exposure) and tolerance (percent change in ST50 in a second exposure) towards alcohol in mutants of all 13 Drosophila JmjC demethylases genes. Our data shows that mutations in NO66, lid and KDM3 (JHMD2) alter alcohol resistance and tolerance of flies. Mutations in these three genes cause a reduction in ST50 during an initial exposure to vaporized ethanol. During the second exposure (4hrs after the first), NO66 and lid, showed increased tolerance to alcohol, while KDM3 displays the opposite with a reduction in tolerance. An analysis of interactive networks revealed NO66, lid, and KDM3, interact with snr1, a transcription co-activator involved in dendrite morphogenesis and guidance, that interacts with rho and S both known to regulate behavioral responses to ethanol. These results suggest JmjC demethylases play a significant role modifying alcohol-related behaviors and further studies are needed to determine its effects on addiction.