Flavonoids are specialized metabolites largely widespread in plants where they play numerous roles including defense and signaling under stress conditions. These compounds encompass several chemical subgroups such as flavonols which are one the most represented classes. The most studied flavonols are kaempferol, quercetin and myricetin to which research attributes antioxidative properties and a potential role in UV-defense through UV-screening mechanisms making them critical for plant adaptation to climate change. Despite the great interest in flavonol functions in the last decades, some functional aspects remain under debate. This review summarizes the importance of flavonoids in plant defense against climate stressors and as signal molecules with a focus on flavonols in Mediterranean plant species. The review emphasizes the relationship between flavonol location (at the organ, tissue and cellular scales) and their function as defense metabolites against climate-related stresses. It also provides evidence that biosynthesis of flavonols, or flavonoids as a whole, could be a crucial process allowing plants to adapt to climate change, especially in the Mediterranean area which is considered as one of the most sensitive regions to climate change over the globe.