Reactive oxygen species (ROS) are highly reactive molecules that play crucial roles in cellular signaling and homeostasis. While moderate levels of ROS are essential for various cellular functions, including gene expression, elevated ROS levels can lead to oxidative stress and contribute to several pathologic conditions, such as tumor promotion and progression. However, ROS can also trigger programmed cell death (PCD), making them a double-edged sword in cancer therapy. The review highlights the molecular mechanisms underlying the development of therapeutic strategies that target ROS levels to treat cancer. It emphasizes the role of ROS generated by different metabolic pathways as potential "Trojan horses" to eliminate cancer cells. The authors discuss the complex interplay between ROS production and scavenging in cancer, noting that cancer cells often have increased antioxidant systems, making them more sensitive to further increases in ROS levels. The article also explores the various ways in which ROS induce PCD, including apoptosis, autophagy, and necroptosis. It reviews the recent findings on the role of nuclear ROS in transcription and DNA damage, and how this can be exploited for therapeutic purposes. Finally, the authors conclude that targeting ROS represents a promising approach for future molecular anticancer strategies, with potential for high selectivity and efficacy in cancer treatment.Reactive oxygen species (ROS) are highly reactive molecules that play crucial roles in cellular signaling and homeostasis. While moderate levels of ROS are essential for various cellular functions, including gene expression, elevated ROS levels can lead to oxidative stress and contribute to several pathologic conditions, such as tumor promotion and progression. However, ROS can also trigger programmed cell death (PCD), making them a double-edged sword in cancer therapy. The review highlights the molecular mechanisms underlying the development of therapeutic strategies that target ROS levels to treat cancer. It emphasizes the role of ROS generated by different metabolic pathways as potential "Trojan horses" to eliminate cancer cells. The authors discuss the complex interplay between ROS production and scavenging in cancer, noting that cancer cells often have increased antioxidant systems, making them more sensitive to further increases in ROS levels. The article also explores the various ways in which ROS induce PCD, including apoptosis, autophagy, and necroptosis. It reviews the recent findings on the role of nuclear ROS in transcription and DNA damage, and how this can be exploited for therapeutic purposes. Finally, the authors conclude that targeting ROS represents a promising approach for future molecular anticancer strategies, with potential for high selectivity and efficacy in cancer treatment.