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A common challenge in microbial production of renewable fuels and chemicals is that the process is product-limiting due to the toxicity of produced compounds, which can inhibit or kill the fermenting microorganisms and prematurely halt production. Premature termination of fermentation leads to low concentration of target products, reduced yield and productivity, excessive generation of fermentation effluents, and increased energy costs for product recovery. Therefore, any process or strategy that shields the fermenting microorganisms from the chaotropic effects of their products will increase their longevity and, in turn, enhance product concentration, yield, and productivity. Vacuum-assisted recovery (VAR) is an in-situ product recovery (ISPR) technique that offers a promising strategy for alleviating product toxicity during fermentation. VAR enhances productivity by maintaining the concentration of fermentation products in the bioreactor below toxicity thresholds throughout the process. This chapter presents the current state of research on VAR as an ISPR technique for product removal during fermentation, discussing its underlying mechanisms, integration with fermentation systems, and key operational considerations and challenges. It, therefore, presents the current state of research on VAR as an ISPR technique for butanol or acetone–butanol–ethanol (ABE) removal during fermentation. The chapter also highlights the importance of VAR in ammonia recovery in anaerobic digestion systems. The underlying mechanisms of VAR, integration with fermentation systems, and key operational considerations and challenges are discussed.