Bioethanol and biogas production are the most common fermentation process to convert organic waste into energy. The presence of inhibitory compounds affects the performance of fermentation, leading to lower product yield. The inhibitory compounds for bioethanol and biogas might be different due to the different types of microorganism used for the process, in which bioethanol process uses a single culture, while biogas process uses a mix culture of microorganisms. However, in general, the inhibitors can be classified into three groups. The first group is natural inhibitor exist in the raw material such as flavor compounds or chemical compounds that contaminates available in the waste stream such as heavy metals, light metals, antibiotics, and pesticides. The second group is inhibitor that forms during the fermentation process such as ammonia, sulfide, and ethanol. The third group is inhibitor which is formed during the pretreatment of lignocellulose such as furfural, hydroxymethylfurfural, phenolic compounds, and humic acid. The minimum inhibitory concentration and inhibition mechanism will be discussed in this chapter. The inhibition effects can be reduced or removed by choosing a suitable concentration of the substrates and choosing a proper method for the pretreatment and/or hydrolysis steps. When the toxic compounds are available in the substrate, detoxification could be an option, although it has some expenses and might lead to partial loss of sugars. However, choosing a right strategy for the fermentation by selecting a suitable process, for example, fed-batch or continuous mode with high cell density or encapsulated cells, using a tolerant organism or an organism that can convert the inhibitors, might avoid the necessity of detoxification.