The exceptional and original features of microorganisms and their natural and biosynthetic capacities make them the ideal technology to solve many of the difficult problems today. They have a role in both scientific research and other fields of exploration, particularly when they work under certain specific environmental and cultural conditions. Over last seven decades, the use of beneficial microorganisms has contributed significantly to the advancement of several fields, including food fermentation, biomedicine, environmental protection, bioenergy, modern agriculture, and the efficient treatment of agricultural and urban waste. Many of these technological advances would not have been possible through the use of simple methods of chemical and physical engineering and, if they had occurred, these developments would not have been practical or economically viable. Even though the application of microbial technologies in recent years has successfully solved various agricultural and environmental problems, the scientific community has not accepted them due to the difficulties of reproducibility of the expected results. Microbial technology is only effective when applied under optimal culture conditions for production of the specific metabolites. Yet the provision in the market for microbial inoculants has increased rapidly due to these new technologies. Most important advances have emerged in areas where the microbial technology is efficiently supported by the marketing of produced metabolites. A great opportunity for microbial technology is the substitution of biopesticides, which are being widely used in modern organic agriculture, for the use of fertilizers and chemical pesticides. This chapter describes the general principles, advances, and challenges of microbial technology, placing emphasis on culture selection, laboratory assays, instrumentation, process control, product recovery, reuse of biocatalysts, bioeconomic trends, patents, and fermentation processes for the agricultural, food, pharmaceutical, soft chemistry, energy, and environmental sectors.