Prominin-1 or otherwise known as CD133 is a glycoprotein that is present in humans and mice. Since the first description of prominin in 1997, in mouse neuroepithelial cells and in human hematopoietic stem cells as AC133 antigen, this molecule has aroused a large interest especially, as a stem cell marker, that gave rise to an ever growing body of publications and more recently its expression in cancer stem cells. Controversies as to its role as a cancer stem and its detection in different models, as well as its use as a prognostic marker have emerged. Yet, beyond its use as a stem cell and cancer stem cell marker, prominin-1/CD133 displays unique biological features and appears of importance in other processes like for example in retinal biogenesis. Indeed, this five-transmembrane plasma membrane glycoprotein, which marks membrane protrusions is associated with several essential processes like cell polarity, asymmetric cell division and membrane remodeling. We propose to review current knowledge about this intriguing molecule and present pertinent information to determine the biological role of prominins and assess their importance in medicine and cancer research. The primary audience for this book is geared towards scientists and researchers with interest in cancer stem cells, stem cells, cell biology, neurobiology, and regenerative medicine.