Micronuclei are small membrane-bounded compartments with a DNA content encapsulated by a nuclear envelope and spatially separated from the primary nucleus. Micronuclei have long been linked to chromosome instability , genome rearrangements, and mutagenesis . They are frequently found in cancers, during senescence, and after genotoxic stress. Compromised integrity of the micronuclear envelope delays or disrupts DNA replication , inhibits DNA repair , and exposes micronuclear DNA directly to cytoplasm. Micronuclei play a central role in tumorigenesis, with micronuclear DNA being a source of complex genome rearrangements (including chromothripsis) and promoting a cyclic GMP–AMP synthase (cGAS)-mediated cellular immune response that may contribute to cancer metastasis . Here, we discuss recent findings on how micronuclei are generated, what the consequences are, and what cellular mechanisms can be applied to protect against micronucleation.