Successful weed management in agroecosystems centers on manipulating the weed seed bank in soil, the source of annual weed infestations. Despite advances in aboveground weed control and decreases in the production of new seed, weed infestations continue to be generated from a small portion of the seed bank that persists as a result of dormancy and resistance to decay. Depletion of the persistent seeds using soil-applied chemicals to stimulate germination has received much attention while the search for microorganisms selective for seed decay has been largely overlooked. This paper provides an overview of the effects of microorganisms on weed seed viability relative to seed bank depletion, and how this information can be applied to weed management. Limited studies indicate that microorganisms associated with weed seeds can contribute to seed bank depletion through attraction to seeds by chemotaxis, rapid colonization of the spermosphere and production of enzymes and/or phytotoxins to kill seeds prior to germination. It is recognized, however, that the best opportunity for success will be through integration of selected microorganisms or microbial products with other approaches including germination stimulation, application of low rates of herbicides, manipulation of the soil environment (e.g., solarization), and biological control agents for effectively eliminating dormant, persistent seeds from soil. To achieve success, more in-depth research on microbial factors affecting weed seed banks is required.