Sp/KLF family members, of which at least 20 distinct nuclear proteins are known to date, serve as transcription factors by binding to GC-enriched sites within target gene promoters. These molecules regulate diverse cellular processes such as proliferation, differentiation, and apoptosis, via their interactions with various other nuclear proteins in promoter- and cell-context-dependent pathways to effect transactivation or transrepression. Recent studies indicate that Sp-family members may functionally interact with ligand-activated nuclear receptors, especially those for steroid hormones. This review provides a discussion of the putative mechanisms and important participants involved in the crosstalk between selected members of this family and the receptor for the pregnancy hormone progesterone, and the relevant outcomes to the control of the transcriptional network in the uterine endometrium.