The pretreatment of raw materials is necessary for ethanol production from lignocellulose, however, a variety of compounds which inhibit the fermenting microorganism such as Saccharomyces cerevisiae are inevitably formed in this bioprocess. Based on their chemical properties, the inhibitors are usually divided into three major groups: weak acids, furaldehydes and phenolic compounds. These compounds negatively affect the growth of S. cerevisiae, ethanol yield and productivity, which is one of the significant hurdles for the development of large-scale ethanol production from lignocellulose. We address here the origins of the three kinds of inhibitors and their mechanisms to S. cerevisiae. We also discuss the strategies of improving the fermentation performance of yeast, including detoxification of the pretreated substrates, enhancement of yeast tolerance and also fermentation control to reduce the effects of the inhibitors. The methods used in enhancing the yeast tolerance are traditional mutagenic breeding integrated with strains evolution under the suitable selective pressure, and metabolic engineering by introducing and/or overexpressing genes encoding enzymes such as furfural reductase, laccase and phenylacrylic acid decarboxylase, that confer the S. cerevisiae strains resistance towards specific inhibitors.