Transcriptional activators are currently thought to consist of 40–80 amino acid tracts that promote target gene expression through multiple contacts with proteins in the transcriptional apparatus. However, little is known about the sequence and structural requirements of minimal mammalian activation domains. On page 1080, Frangioni et al. describe the results of a phage display screen of a library of eight–amino acid peptides for binding to the KIX domain of the transcriptional co-activators p300 and CBP. The peptides identified were capable of mediating transcriptional co-activation when fused to a DNA-binding domain. The results suggest that these minimal activation domains might be engineered to create precise activators for transcription factor-mediated gene therapy.