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Drought stress affects growth, morphological and biochemical properties in plants. To develop resistance and adapt to drought, plants need metabolic changes. Adaptations to stress involve changes to gene expression that activate metabolic processes that promote drought resistance and that may include biosynthesis and accumulation of specialized metabolites. Such adaptations in specialized metabolism may be important mechanisms leading to plant stress resistance and involve production of phenolics, flavonoids, terpenoid and nitrogen containing compounds that are species and genotype specific. Most plants having special metabolites to adapt to drought stress belong to different botanical families. C3, C4 and CAM plants, apply both morphological and metabolic mechanisms to adapt to drought as well as to accumulate specialized metabolites. Generally, medicinal plants increase their functional metabolites content, when exposed to drought stress. During drought stress, transcription factors and related pathways for biosynthesis of phenolics, flavonoids, anthocyanins as well as for stress jasmonate and abscisic acid stress hormones are activated.