The use of non-genetically modified microbial inoculants for beneficial purposes in agriculture, bioremediation, medicine, and infrastructure is increasing. The intentional introduction of plants and animals for similar purposes has a long history, but despite successes, has resulted in thousands of plant and animal species becoming invasive, with catastrophic consequences for the environment, public health, and society. Hundreds of microbial invasions are known, and although microbial inoculants can provide benefits, they have similar potential to negatively impact ecosystems. Little action has been taken to guard against the threat of microbial invasions from non-genetically modified microbial inoculants. Now is the time to develop an effective research and management infrastructure for these microbial inoculants to avoid catastrophic outcomes similar to those caused by intentionally-introduced plants and animals. Here, we propose a unified research and management approach to spur action by regulators and practitioners. Three aims need to be addressed: developing (1) a coherent mechanistic understanding of how microbial inoculants effect invasions, (2) predictive models forecasting which microbes pose risks of invasion, and (3) effective management strategies. To guide mechanistic understanding, we develop seventeen key hypotheses. For predictive modeling, quantitative trait analysis and risk maps will be critical. Management strategies will depend on both understanding and predictions, but prevention rather than eradication or control of invasive microbes is likely to be most effective, and a precautionary regulatory approach should immediately be applied to inoculants. Multiple data types will be instrumental for understanding and predicting which microbial inoculants have invasive potential: experimental data from microcosm and mesocosm experiments, and large-scale observational data from microbial surveillance. Both phenomenological and mechanistic modeling approaches will be key in achieving these fundamental and applied research aims. Moreover, each stage of the invasion process --- transport, establishment, spread, and impacts --- often need to be investigated separately. The unified approach developed here provides a roadmap for developing a research and management infrastructure to guard against the threat of microbial invasions from non-genetically modified microbial inoculants.