Prokaryotic and eukaryotic microbes thrive successfully in stressful environments such as high osmolarity, acidic or alkali, solar heat and u.v. radiation, nutrient starvation, oxidative stress, and several others. To live under these continuous stress conditions, these microbes must have mechanisms to protect their proteins, membranes, and nucleic acids, as well as other mechanisms that repair nucleic acids. The stress responses in bacteria are controlled by master regulators, which include alternative sigma factors, such as RpoS and RpoH. The sigma factor RpoS integrates multiple signals, such as the general stress response regulators and the sigma factor RpoH regulates the heat shock proteins. These response pathways extensively overlap and are induced to various extents by the same environmental stresses. In eukaryotes, two major pathways regulate the stress responses: stress proteins, termed heat shock proteins (HSP), which appear to be required only for growth during moderate stress, and stress response elements (STRE), which are induced by different stress conditions and these elements result in the acquisition of a tolerant state towards any stress condition. In this review, the mechanisms of stress resistance between prokaryotic and eukaryotic microbes will be described and compared.