In stem cells, cell polarity is required for the asymmetric localization of cell fate determinants and for proper spindle orientation, resulting in the formation of two unequal daughter cells upon asymmetric cell division (ACD). In most cases, one of the two daughter cells formed upon ACD will again be a stem cell, while the second one undergoes differentiation, either directly or after a few additional divisions. Defects in the control of cell polarity and ACD can cause premature differentiation and loss of the stem cells, or over-proliferation resulting in tumor formation. Work by us and others has shown that polarity and ACD of different types of stem cells in the fruit fly is controlled by evolutionarily conserved molecular mechanisms. Most notably, the PAR-complex is required for cortical polarity in neural stem cells. More recently, we have started to analyze the regulatory transcriptional networks functioning upstream of the polarity regulators in different types of stem cells.