Both immune and non-immune cells express an extensive array of scavenger receptors that bind a variety of ligands including bacterial cell-wall components and lipoproteins. Over the past several years, significant advances have been made in elucidating the role of scavenger receptors, predominantly Class A scavenger receptors SR-A I/II and MARCO, on macrophages in the binding of environmental particles such as crystalline silica and titanium dioxide. Recent evidence indicates that the binding of crystalline silica to scavenger receptors leads to apoptosis of macrophages and release of mediators (e.g., proinflammatory cytokines) contributing to lung inflammation and fibrosis. In this review, we examine the evidence for the role of SR-A I/II and MARCO in binding of the environmental particles and signaling initiated by particle-receptor interaction. Emerging concepts on the molecular details of signaling cascades by engagement of scavenger receptors by the environmental particles are also discussed.