Introduced microorganisms are potentially powerful agents for manipulation of processes and/or components in soil. Fields of application include enhancement of crop growth, protection of crops against plant-pathogenic organisms, stimulation of biodegradation of xenobiotic compounds (bioaugmentation), and improvement of soil structure. Inoculation of soils has already been applied for decades, but it has often yielded inconsistent or disappointing results. This is caused mainly by a commonly observed rapid decline in inoculant population activity following introduction into soil, i.e., a decline of the numbers of inoculant cells and/or a decline of the (average) activity per cell. In this review, we discuss the available information on the effects of key factors that determine the fate and activity of microorganisms introduced into soil, with emphasis on bacteria. The factors addressed include the physiological status of the inoculant cells, the biotic and abiotic interactions in soil, soil properties, and substrate availability. Finally, we address the possibilities available to effectively manipulate the fate and activity of introduced microorganisms in relation to the main areas of their application.