We are continuously exposed to large numbers of non-biological, persistent particulates through dermal, oral and inhalation routes. At sizes perfect for cell interactions, such modern particle exposures are derived from human engineering either purposefully (e.g. additives/excipients) or inadvertently (e.g. pollution). Whether oral or dermal exposure to common particles has significantly adverse effects is not yet known. However, relationships between increased morbidity or mortality and airborne particle exposure are well established. Large nanoparticles and microparticles adsorb environmental molecules, including antigens and allergens, and deliver them to cells potentially with an adjuvant effect. Smaller nanoparticles may have enhanced redox activity due to increased surface areas or band gap effects. Under some circumstances, ultrasmall nanoparticles can ligate cellular receptors or interact with other cell machinery and drive distinct cell signalling. These, as well as the potential for inflammasome activation, are discussed as feasible pathways to understanding or de-bunking particle toxicity.