In plant–microbe interactions, symbionts and pathogens live within plants and attempt to avoid triggering plant defense responses. In order to do so, these microbes have evolved multiple mechanisms that target components of the plant cell nucleus. Rhizobia-induced symbiotic signaling requires the function of specific legume nucleoporins within the nuclear pore complex. Symbiont and pathogen effectors harbor nuclear localization sequences that facilitate movement across nuclear pores, allowing these proteins to target transcription factors that function in defense. Oomycete pathogens introduce proteins that interact with plant pre-mRNA splicing components in order to alter host splicing of defense-related transcripts. Together, these functions indicate that the nucleus is an active site of symbiotic and pathogenic functioning in plant–microbe interactions.