Ferroptosis is a non-apoptotic form of cell death triggered by conditions that inhibit glutathione biosynthesis or the antioxidant enzyme glutathione peroxidase 4 (GPX4). This process is characterized by iron-dependent accumulation of lipid reactive oxygen species (L-ROS) and depletion of plasma membrane polyunsaturated fatty acids (PUFAs). Cancer cells with high RAS-RAF-MEK pathway activity or p53 expression may be particularly susceptible to ferroptosis. Small molecule inhibitors of ferroptosis, such as ferrostatin-1 and liproxstatin-1, have been identified and can block pathological cell death in various tissues. Recent studies have identified several genes involved in ferroptosis, including those related to lipid and amino acid metabolism. Key questions include the relationship between ferroptosis and other forms of cell death, and whether the activation or inhibition of ferroptosis can be exploited for therapeutic purposes.Ferroptosis is a non-apoptotic form of cell death triggered by conditions that inhibit glutathione biosynthesis or the antioxidant enzyme glutathione peroxidase 4 (GPX4). This process is characterized by iron-dependent accumulation of lipid reactive oxygen species (L-ROS) and depletion of plasma membrane polyunsaturated fatty acids (PUFAs). Cancer cells with high RAS-RAF-MEK pathway activity or p53 expression may be particularly susceptible to ferroptosis. Small molecule inhibitors of ferroptosis, such as ferrostatin-1 and liproxstatin-1, have been identified and can block pathological cell death in various tissues. Recent studies have identified several genes involved in ferroptosis, including those related to lipid and amino acid metabolism. Key questions include the relationship between ferroptosis and other forms of cell death, and whether the activation or inhibition of ferroptosis can be exploited for therapeutic purposes.