The nucleus, at the heart of the eukaryotic cell, hosts and protects the genetic material, governs gene expression and regulates the whole cell physiology, including cell division. A growing number of studies indicate that various animal and plant pathogenic bacteria can deliver factors to this central organelle to subvert host defences by directly interfering with transcription, chromatin-remodelling, RNA splicing or DNA replication and repair. Such bacterial molecules entering the nucleus, which we propose to term ‘nucleomodulins’, use diverse strategies to hijack nuclear processes by targeting host DNA or an array of nuclear proteins. In some cases, bacteria can even enter the nucleus. These bacterial ‘nuclear attacks’ might have permanent genetic or long-term epigenetic effects on the host. Studying nucleomodulins and endonuclear bacteria can thus generate new insights into long-term impacts of infectious diseases and create novel tools for biotechnological applications and for deciphering the regulation of nuclear dynamics.