Specificity protein 1 (Sp1) and other Sp and Krüppel-like factor (KLF) proteins are members of a family of transcription factors which bind GC/GT-rich promoter elements through three C(2)H(2)-type zinc fingers that are present at their C-terminal domains. Sp1-Sp4 proteins regulate expression of multiple genes in normal tissues and tumours. There is growing evidence that some Sp proteins play a critical role in the growth and metastasis of many tumour types by regulating expression of cell cycle genes and vascular endothelial growth factor. Sp/KLF proteins are also potential targets for cancer chemotherapy.