The review discusses the challenges and solutions related to the bioconversion of lignocellulosic feedstocks into biofuels, chemicals, and polymers through microbial fermentation. The process typically involves an acidic thermochemical pretreatment step to enhance enzymatic hydrolysis of cellulose. However, this pretreatment generates inhibitors that inhibit both enzymatic hydrolysis and microbial fermentation. The review highlights the formation of various inhibitors, including aromatic compounds, aliphatic acids, furan aldehydes, inorganic ions, and bioalcohols, and their impact on microbial growth and product yield. It also explores methods to mitigate these inhibitors, such as conditioning slurries and hydrolysates, and the use of reducing agents for in-situ detoxification. Additionally, the review covers strategies for improving the performance of both enzymatic and microbial biocatalysts, including genetic engineering and the development of hyperresistant microbial strains. The overall goal is to enhance the efficiency and sustainability of lignocellulosic bioconversion processes.The review discusses the challenges and solutions related to the bioconversion of lignocellulosic feedstocks into biofuels, chemicals, and polymers through microbial fermentation. The process typically involves an acidic thermochemical pretreatment step to enhance enzymatic hydrolysis of cellulose. However, this pretreatment generates inhibitors that inhibit both enzymatic hydrolysis and microbial fermentation. The review highlights the formation of various inhibitors, including aromatic compounds, aliphatic acids, furan aldehydes, inorganic ions, and bioalcohols, and their impact on microbial growth and product yield. It also explores methods to mitigate these inhibitors, such as conditioning slurries and hydrolysates, and the use of reducing agents for in-situ detoxification. Additionally, the review covers strategies for improving the performance of both enzymatic and microbial biocatalysts, including genetic engineering and the development of hyperresistant microbial strains. The overall goal is to enhance the efficiency and sustainability of lignocellulosic bioconversion processes.