Nitrogen (N) and Water (W) are crucial inputs for plant survival as well as

costly resources for agriculture. Given their importance, the molecular

mechanisms that plants rely on to signal changes in either N or W status have

been under intense scrutiny. However, how plants sense and respond to the

combination of N and W signals at the molecular level has received scant

attention. The purpose of this review is to shed light on what is currently

known about how plant responses to N are impacted by W status. We review classic

studies which detail how N and W combinations have both synergistic as well as

antagonistic effects on key plant traits, such as root architecture and stomata

aperture. Recent molecular studies of N and W interactions show that mutations

in genes involved in N-metabolism affect drought responses, and vice versa.

Specifically, perturbing key N-signaling genes may leads to changes in drought

responsive gene expression programs, which is supported by a meta-analysis we

conduct on available transcriptomic data. Additionally, we cite studies that

show how combinatorial transcriptional responses to N and W status might drive

crop phenotypes. Through these insights, we suggest research strategies that

could help develop crops adapted to marginal soils depleted in both N and W, an

important task in the face of climate change.