Microbial endophytes are symbionts dwelling within plant tissues without appearance of disease symptoms on host plant and have been recently investigated for their plant growth-promoting properties and their beneficial functions associated with plant responses under abiotic stress conditions. This study focuses on the critical role of endophytic microbes in plant health and their stimulatory different mechanisms to tolerance against abiotic stress in plants. Endophytic microbial community can enhance plant growth through producing secondary active compounds which protect the plant from pathogens such as insect and fungi; also endophytes can produce extracellular enzymes which play critical roles in colonization of endophytes within the plant host. Microbial endophytes have the ability to act as plant growth-promoting agents through producing phytohormones and also enable plants to grow in contaminated soils through breakdown of hazardous compounds. Endophytes manage plant growth under adverse conditions such as salinity, drought, temperature, heavy metal stress, and nutrient stress through different mechanisms. This chapter may introduce new approaches for the use of endophytic inoculants to combat abiotic stresses in agricultural fields, which increases global crop production.