High-energy heavy-ion beams deposit dense energy along their trajectory when they hit a target. This characteristic energy deposition induces a variety of changes in the living organisms that are specific to heavy ions. However, when attempting to elucidate the mechanism of this biological effect from a molecular biological perspective, the heterogeneity of microdosimetric energy deposition becomes an obstacle to analyses. For this reason, heavy-ion microbeam irradiation technologies have been developed that form microscopic heavy-ion beam spots in the micrometer range, allowing biological samples to be targeted and irradiated under atmospheric conditions. In this chapter, it will first discuss what microdosimetric phenomena occur when heavy ions hit living organisms and what life science research problems they raise. Next, a heavy-ion microbeam systems capable of irradiating living organisms will be described, which was developed to overcome this problem and to elucidate the hit effect of heavy ions on living organisms. Finally, unique life science research related to heavy ions achieved by using those heavy-ion microbeam devices will be outlined.