The significant amounts of reactive oxygen species (ROS), mainly superoxide anion (O2*-), are produced each day in the human body. ROS play many important and beneficial functions, but they can also contribute to the development of many diseases, including those with atherosclerotic background. Vascular and phagocytic NADPH oxidases are a multicomponent enzymatic complexes which are the main source of O2*- in the vasculature. The p22phox subunit plays an important role in the functioning of these enzymes and is encoded by the CYBA gene (cytochrome b-alpha). In recent years, it was shown the presence of multiple genetic polymorphisms in the CYBA gene, including variants: -930A>G, -852C>G, -675A>T, -536C>T, *24A>G, 521C>T and 214C>T. The functional and association studies were conducted in many research centers from around the world, as a result of these findings. The aim of the present study was to summarize of the available information on the CYBA gene, function of its polymorphisms and their associations with atherosclerosis-related diseases.