Endophytes are hidden microorganisms that live symbiotically and asymptomatically in the intracellular compartments of green plants, and their co-existence gives a beneficial effect on hosts’ survival, growth, and metabolism. Endophytes are ubiquitous in occurrence and are reported from almost every plant studied till date. Endophytic fungi, bacteria, and actinobacteria constitute the rich pool of plants’ internal ecosystem and open up a new domain of Endophyte Biology. The innumerable occurrence of endophytes has made them a potent biotechnological tool to solve environmental as well as industrial/pharmaceutical problems. Though each and every type of plant holds endophytes, here the focus has been given on medicinal plants only. Medicinal plants contain phytochemicals that have curative properties, which have been used to treat diseases from time immemorial and are an invaluable source of medicines. Endophytic colonization increases levels of phytohormones, modulates the antioxidant system, improves nutrient uptake, and also ameliorates the effects of environmental stress by increasing productivity and resisting plant pathogens by strengthening the immune system. They build more sustainable and environmentally friendly agricultural practices. Biotic and abiotic stress/problems like increased temperature, low precipitation, high soil salinity, and improper use of synthetic chemicals reduce soil fertility. These environmental factors and plant pathogens affect the growth of agricultural crops. This needs to be tackled immediately, and endophytes along with their metabolites play a major role here. In this chapter, we enumerate the diversity of endophytes from medicinal plants and their potential to reduce abiotic and biotic stress in agricultural crop plants.