A fundamental feature of the transcriptional response to an nuclear factor‐κB (NF‐κB)‐inducing stimulus is that the response is highly selective and limited to the activation of only a subset of potential NF‐κB target genes. One major contributor to selectivity of the response is likely to be the capacity of different NF‐κB dimers to regulate different sets of target genes. The NF‐κB family of transcription factors consists of five proteins, RelA, c‐Rel, RelB, p50, and p52, which assemble into several homodimeric and heterodimeric species. Studies of mutant mouse strains have revealed that each family member, and perhaps each dimer, carries out unique functions in regulating transcription in cells of the immune system and in many other cell types. Dimer‐specific functions can be conferred by selective protein–protein interactions with other transcription factors, coregulatory proteins, and chromatin proteins. Unique DNA‐binding specificities and affinities make additional contributions to selectivity of the response, with growing evidence that some NF‐κB dimers can adopt different conformations and thereby function differently when bound to different DNA sequences. Despite significant advances, our knowledge remains limited and many years of additional work will be needed to fully understand how the dimer‐specific functions of NF‐κB contribute to transcriptional selectivity.