Increasing vulnerability of crops to a wide range of abiotic and biotic stresses can have a marked influence on the growth and yield of major crops, especially sugarcane (Saccharum spp.). In response to various stresses, plants have evolved a variety of complex defense systems of signal perception and transduction networks. Transcription factors (TFs) that are activated by different pathways of signal transduction and can directly or indirectly combine with cis-acting elements to modulate the transcription efficiency of target genes, which play key regulators for crop genetic improvement. Over the past decade, significant progresses have been made in deciphering the role of plant TFs as key regulators of environmental responses in particular important cereal crops; however, a limited amount of studies have focused on sugarcane. This review summarizes the potential functions of major TF families, such as WRKY, NAC, MYB and AP2/ERF, in regulating gene expression in the response of plants to abiotic and biotic stresses, which provides important clues for the engineering of stress-tolerant cultivars in sugarcane.