This review discusses the challenges and solutions related to the bioconversion of lignocellulose, focusing on inhibitors formed during acidic thermochemical pretreatment and methods to detoxify them. Lignocellulosic feedstocks, including agricultural residues, forestry waste, and energy crops, are rich in cellulose, hemicellulose, and lignin. Pretreatment with strong acids or enzymes enhances enzymatic hydrolysis, but generates inhibitors such as phenolic compounds, aliphatic acids, and furan aldehydes that hinder microbial fermentation and enzyme activity. These inhibitors include sugars like cellobiose and glucose, ethanol, and furfural, which can inhibit yeast growth and ethanol production. Inhibitors are formed during pretreatment, leading to the release of various compounds, including phenolics, aliphatic acids, and furan aldehydes. These compounds can be toxic to microorganisms and enzymes, reducing the efficiency of bioconversion. Strategies to mitigate these issues include chemical detoxification using reducing agents, enzymatic or microbial biocatalysts, and conditioning of slurries and hydrolysates. Alkaline treatment, such as overliming with calcium hydroxide or sodium hydroxide, is effective in reducing inhibitor levels and improving fermentation efficiency. However, it can also affect sugars, potentially reducing ethanol yields. Genetic engineering of yeast strains to enhance resistance to inhibitors is another approach. For example, overexpression of transcription factors like Yap1 or multidrug resistance proteins can improve yeast tolerance to phenolics, furan aldehydes, and aliphatic acids. Additionally, in-situ detoxification during fermentation using reducing agents can help mitigate inhibitor effects. The review highlights the importance of managing inhibition problems in the bioconversion of lignocellulosic feedstocks. Effective detoxification methods, such as alkaline treatment, enzymatic biocatalysts, and genetic engineering, are crucial for improving ethanol yields and overall process efficiency. The integration of these strategies is essential for the successful commercialization of lignocellulosic biofuels.This review discusses the challenges and solutions related to the bioconversion of lignocellulose, focusing on inhibitors formed during acidic thermochemical pretreatment and methods to detoxify them. Lignocellulosic feedstocks, including agricultural residues, forestry waste, and energy crops, are rich in cellulose, hemicellulose, and lignin. Pretreatment with strong acids or enzymes enhances enzymatic hydrolysis, but generates inhibitors such as phenolic compounds, aliphatic acids, and furan aldehydes that hinder microbial fermentation and enzyme activity. These inhibitors include sugars like cellobiose and glucose, ethanol, and furfural, which can inhibit yeast growth and ethanol production. Inhibitors are formed during pretreatment, leading to the release of various compounds, including phenolics, aliphatic acids, and furan aldehydes. These compounds can be toxic to microorganisms and enzymes, reducing the efficiency of bioconversion. Strategies to mitigate these issues include chemical detoxification using reducing agents, enzymatic or microbial biocatalysts, and conditioning of slurries and hydrolysates. Alkaline treatment, such as overliming with calcium hydroxide or sodium hydroxide, is effective in reducing inhibitor levels and improving fermentation efficiency. However, it can also affect sugars, potentially reducing ethanol yields. Genetic engineering of yeast strains to enhance resistance to inhibitors is another approach. For example, overexpression of transcription factors like Yap1 or multidrug resistance proteins can improve yeast tolerance to phenolics, furan aldehydes, and aliphatic acids. Additionally, in-situ detoxification during fermentation using reducing agents can help mitigate inhibitor effects. The review highlights the importance of managing inhibition problems in the bioconversion of lignocellulosic feedstocks. Effective detoxification methods, such as alkaline treatment, enzymatic biocatalysts, and genetic engineering, are crucial for improving ethanol yields and overall process efficiency. The integration of these strategies is essential for the successful commercialization of lignocellulosic biofuels.