Stomata control the exchange of CO 2 and water in land plants. For this reason, plants evolved to quickly respond the surrounding environment and endogenous cues in order to maintain their photosynthetic rates, but avoiding excessive water loss. Although guard cell has been used as model for characterization of signaling pathways, mainly regarding abscisic acid (ABA) response, several important questions about its functioning remain elusive. Recently, transcriptomics, proteomics, and metabolomics studies carried out using guard cells as model have contributed substantially for our understanding on how guard cells sense and respond to relative air humidity, CO 2 , ABA, and sucrose. Comparatively, proteomics and metabolomics platforms need substantial improvement to increase the number of analytes detected. However, with the introduction of metabolomics-based technologies, several studies have been published increasing our knowledge on guard cell function. Here, we review these new exciting findings as well as discuss the importance of using these new data to improve prediction when modelling stomatal behavior.