Transcription factors (TF) play a key role in certain mechanisms by which specific genes are expressed in a temporal and tissue-specific manner. Understanding those mechanisms is still a challenging question in biology. Their modular organization allows the possibility of classifying them based on the structure of the domains that bind DNA or interact with other proteins. Those domains not only define the different TF families but also provide insights into the biological functions played by them. Among these, the POK (Poxviruses and Zinc-finger (POZ) and Krüppel) family of transcription repressors is characterized by the presence in their structures of an amino-terminal POZ/Broad Complex, Tramtrack, and Bric à brac (BTB) domain and several Krüppel-type zinc fingers at the carboxy-terminal moiety. The POZ/BTB domain mediates homo- and heterodimerization as well as protein-protein interactions, allowing the recruitment of corepressor complexes. On the other hand, the specific zinc fingers mediate specific DNA sequences recognition and binding. In the last few years, several reports have highlighted the importance that this family of transcriptional repressors plays in different processes such as cancer, development and stem cell biology.