Plants are incessantly exposed to a wide range of abiotic stress factors. Drought is one of the major environmental stress agents, which negatively affects the growth and development of plants. Plants evolved a variety of protective mechanisms leading to stress resistance. Tolerance of drought stress is due to plant response at the molecular, physiological, cellular, tissue, and whole organism levels. One of the pivotal plant responses to water deficit is alteration in genes expression profile, including stress response genes and accumulation of their protein products, which enables plants to adapt to drought. Regulation of gene expression under drought stress includes activity of transcription factors belonging to bZIP, AP2/EREBP, NAC, MYB/MYC, NF-Y, ZF-HD, ZFP and WRKY families. Results, published in recent years, demonstrate the significance of mechanisms of the genes expression regulation under drought stress, such as epigenetic modifications including DNA methylation, histones modifications, and genes silencing by micro RNAs. The aim of this paper is to overview the current state of knowledge of regulatory mechanisms controlling gene expression mediated by transcription factors as well as epigenetic mechanisms as the molecular basis of plant tolerance to drought stress.