This review article explores the dual role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in both physiological and pathological conditions. ROS and RNS can cause oxidative damage and tissue dysfunction, but they also serve as molecular signals that activate stress responses beneficial to the organism. Mitochondria have been traditionally thought to play a major role in tissue oxidative damage and dysfunction, but recent data suggest that other cellular sources of ROS also contribute significantly. The interplay between different ROS sources, including mitochondria, peroxisomes, endoplasmic reticulum, and plasma membrane, is highlighted. The article discusses the mechanisms by which ROS and RNS can activate each other, leading to a positive feedback loop that exacerbates oxidative stress and tissue damage. Examples of how ROS and RNS contribute to various pathological conditions, such as cardiovascular disease, diabetes, and neurodegenerative disorders, are provided. The review also examines the role of ROS sources in oxidative stress and tissue dysfunction, emphasizing the importance of mitochondrial function and the potential of other cellular sources in contributing to these conditions.This review article explores the dual role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in both physiological and pathological conditions. ROS and RNS can cause oxidative damage and tissue dysfunction, but they also serve as molecular signals that activate stress responses beneficial to the organism. Mitochondria have been traditionally thought to play a major role in tissue oxidative damage and dysfunction, but recent data suggest that other cellular sources of ROS also contribute significantly. The interplay between different ROS sources, including mitochondria, peroxisomes, endoplasmic reticulum, and plasma membrane, is highlighted. The article discusses the mechanisms by which ROS and RNS can activate each other, leading to a positive feedback loop that exacerbates oxidative stress and tissue damage. Examples of how ROS and RNS contribute to various pathological conditions, such as cardiovascular disease, diabetes, and neurodegenerative disorders, are provided. The review also examines the role of ROS sources in oxidative stress and tissue dysfunction, emphasizing the importance of mitochondrial function and the potential of other cellular sources in contributing to these conditions.