The United Nations Environment Programme (UNEP/WHO) defines particulate matter (PM) as a mixture of solid or liquid particles suspended and dispersed in the air. Constituted by a complex mixture of organic and inorganic components like metals, acids, soil, and dust is considered a major human carcinogen present in air pollution. When inhaled, PM particles penetrate the respiratory tract, where they affect different organs and systems depending on their aerodynamic size and chemical properties. In the organism, this cocktail-like mixture can interact with cellular mechanisms related to the production of reactive oxygen species (ROS) and can cause damage to important macromolecules such as DNA, lipids, and proteins. Additionally, PM induces a variety of effects at a cellular level, such as inflammation, DNA damage, and genomic instability, acting as a driving force of carcinogenic processes and increasing the incidence of respiratory, cardiopulmonary, neurogenerative, and neurodevelopment disorders. This book chapter reviews the main characteristics of PM, its effects on health, and its role in genomic instability and associated molecular mechanisms. Additionally, we explore different biomarkers associated with PM exposure, DNA damage, and the influence of PM-related oxidative stress in disease development.