Over the past six decades, the concept of "redox" was focused on one arm of the redox spectrum: oxidative stress. In fact, a vast majority of experimental and clinical studies addressing redox mechanisms claimed "oxidative stress" as the culprit for acute or chronic disease conditions. Recent studies have documented that reactive oxygen species (ROS) are crucial signaling molecules facilitating various cellular processes. Thus, abrogation of these key ROS signaling through abundant antioxidant systems will result in detrimental effects. This Forum highlights the emerging concepts and related mechanisms of the other extreme of the redox spectrum, known as "reductive stress (RS)." The Forum including original research and review articles discusses the causes and consequences of RS in various biological and pathological conditions such as metabolism, cancer, drug resistance, cardiac hypertrophy, and microbial adaptations.