Crystals, fibers, and other microparticles form inside the body from nutrients or metabolites but also enter the body from outside during environmental or occupational exposures. Altogether crystal and microparticle-related diseases account for numerous medical disorders (1). In some of these disorders, the crystal masses themselves cause the problem, e.g., when stones obstruct the bile ducts or the urinary draining system. In other crystal-immune responses largely account for clinical symptoms and tissue damage, e.g., in gout, silicosis, or asbestosis. This Research Topic in Frontiers of Immunology selected a series of articles focusing on how immune and tissue cells respond to crystals, microparticles, and nanoparticles. Our authors shed light on the recent and ongoing research efforts to unravel the molecular mechanisms underlying particle-related tissue injury, inflammation, and remodeling. We hope the readers of this Research Topic find the content useful to further develop the field, to identify common and particle-specific mechanisms of crystallopathies.