The human NFX1 transcription factor constitutes a group of NFX1-type zinc finger proteins. It forms a central Cys-rich region with several NFX1-type zinc finger domains that have been shown to mediate DNA binding. Proteins with NFX1-type zinc fingers are found in protists, fungi, animals and plants, and may be ubiquitous in eukaryotes. This review discusses the structure and putative roles of NFX1-like proteins, with a focus on human NFX1 and Arabidopsis NFXL1 proteins. By means of manual sequence analysis and application of hidden Markov models, we demonstrate that NFX1-like proteins form a specific RING finger motif with a C(4)HC(3) Zn ligand signature and additional distinct features, suggesting that these proteins function as E3 ubiquitin ligases. Phylogenetic analysis revealed different clades of NFX1-like proteins. The plant proteins group into two distinct clades. The genomes of plants such as rice, Arabidopsis, poplar and grapevine encode one member of each clade, suggesting that the presence of two NFX1-like factors is sufficient in flowering plants. The Arabidopsis proteins presumably fine-tune opposed biotic and abiotic stress response pathways.