Salinity is considered a global threat to agriculture and causes a significant reduction in crop yield. In particular, salinity stress promotes reactive oxygen species (ROS) accumulation and ionic imbalance in cells, leading to oxidative stress and even cell death. A large number of genes which are involved in defense, hormone, carbohydrate and metabolic pathways are down-regulated under salinity stress. Plants respond to salinity stress through a series of physiological and molecular mechanisms including antioxidant enzymes, hormones, defense related genes and signaling pathway activation. Plant defense systems modulate the overproduction of ROS through the activation of stress responsive-genes such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and glutamine synthetase (GS) and transcription factors such as MYBs, WRKY, and ERF. The salt overly sensitive (SOS) pathway is potentially involved in salt stress tolerance. SOS1, SOS3 and SOS2 are required for the oxidative stress tolerance by reducing the uptakes, and inter-cellular and intra-cellular distribution of Na+ and Cl−. This review discusses the discovery of stress-responsive genes and signaling pathways, and summarizes the research progress on the regulatory mechanisms of salinity stress tolerance in plants, which will help accelerate breeding programs for salinity stress tolerance.