The extent to which plants can enhance human life support on other worlds depends on the ability of plants to thrive in extraterrestrial environments using in situ resources. Using samples from Apollo 11, 12 and 17, we show that the terrestrial plant Arabidopsis thaliana germinates and grows in diverse lunar regoliths. However, our results show that growth is challenging; the lunar regolith plants were slow to develop, expressed genes indicative of ionic stresses, and many showed severe stress morphologies. Therefore, although in situ lunar regolith can be useful for plant production in lunar habitats, they are not benign substrates. The interaction between plants and lunar regolith will need to be further elucidated, and likely mitigated, to enable efficient use of lunar regolith for life support.