Reactive oxygen species (ROS) and iron play important roles in the innate immune response. ROS are released by immune cells and are highly reactive and indiscriminately destructive in response to pathogens. In addition, ROS act as signaling molecules and play a role in apoptosis, therefore excessive ROS production can damage host molecules, leading to more harm than benefit for the host. Iron acts as a catalyst for the formation of ROS, therefore, manipulation of iron levels is a way in controlling ROS production. Iron metabolism and ROS production may affect many disease processes and must be tightly regulated for the host to generate an appropriate response. Current researches examine the roles of iron and ROS in various conditions, including neurodegeneration, inflammation, infection and cancer. Therapies directed at regulating ROS production through regulating iron levels are a major focus in these fields today.