Recent plans for human return to the Moon have significantly elevated scientific interest in the lunar environment with emphasis on the science to be done in preparation for the return and while on the lunar surface. Since the return to the Moon is envisioned as a dedicated and potentially longer-term commitment to lunar exploration, questions of the lunar environment and particularly its impact on biology and biological systems have become a significant part of the lunar science discussion. Plants are integral to the discussion of biology on the Moon. Plants are envisioned as important components of advanced habitats and fundamental components of advanced life-support systems. Moreover, plants are sophisticated multicellular eukaryotic life-forms with highly orchestrated developmental processes, well-characterized signal transduction pathways, and exceedingly fine-tuned responses to their environments. Therefore, plants represent key test organisms for understanding the biological impact of the lunar environment on terrestrial life-forms. Indeed, plants were among the initial and primary organisms that were exposed to returned lunar regolith from the Apollo lunar missions. This review discusses the original experiments involving plants in association with the Apollo samples, with the intent of understanding those studies within the context of the first lunar exploration program and drawing from those experiments the data to inform the studies critical within the next lunar exploration science agenda.