In this outline of the most prominent factors involved in particle toxicology, we highlight the differences in the toxic potential among airborne particles and describe what is known about the most notorious toxic agents, such as silica and asbestos. The various biological paths and, consequently, the different outcomes in the health risks associated with inhaled, micron-sized particle and fibers, as well as inhaled nanoparticles, are explained on the basis of form, size, and surface reactivity. The most relevant surface properties addressed here are the potential for free radical generation, the adsorption of endogenous molecules, and the degree of hydrophilicity or hydrophobicity of the various materials.