Brassinosteroids (BRs) are a group of plant-specific steroidal phytohormones, which play fundamental roles in regulating diverse aspects of the plant life cycle including plant growth, development, and stress response. Extensive studies have demonstrated that BRs signaling is involved in plant innate immunity as well as the response to environmental stimuli including extreme temperatures, saline-alkali, and drought. In addition, that the BRs signal interacts with other immune-related signals, constructing a complex signal network to regulate plant−microbe interactions and adaptation to adverse environments, has also been preliminarily explored. A timely and updated review on these progresses is of great significance for understanding BRs functions, improving the BRs regulation network and breeding disease-resistant crops, meantime with higher tolerance to abiotic stresses. Here, we mainly focus on the latest advances in the BRs signal which regulate plant defense and tolerance to abiotic and biotic stresses and then further highlight the crosstalk between the BRs signal and other immune-related or stress response pathways, with an aim to use them to improve crops by transgenic technologies.