We reviewed the effect of lunar dust (regolith) on humans by the combination of the hazard/exposure of regolith and microgravity of the moon. With regard to the physicochemical properties of lunar dust, the hazard-related factors are its components, fibrous materials and nanoparticles. Animal exposure studies have been performed using a simulant of lunar dust, and it was speculated that the harmful effects of the simulant lies between those of crystalline silica and titanium dioxide. Fibrous materials may not have a low solubility judging from their components. The nanoparticles in lunar dust may have harmful potentials from the view of the components. As for exposure to regolith, there is a possibility that particles larger than ones in earth (1 gravity) are respirable. In microgravity, 1) the deposition of particles of less than 1 μm in diameter in the human lung did not decrease, 2) the functions of macrophages including phagocytosis were suppressed, 3) pulmonary inflammation was changed. These data on hazard/exposure and microgravity suggest that fine and ultrafine particles in regolith may have potential hazards and risks for humans.