Most cells are polarized. Embryonic and stem cells can use their polarity to generate cell diversity by asymmetric cell division, whereas differentiated cells use their polarity to execute specific functions. For example, fibroblasts form an actin-rich leading edge required for cell migration, neurons form distinctive axonal and dendritic compartments important for directional signaling, and epithelial cells have apical and basolateral cortical domains necessary for maintaining tissue impermeability. It is well established that actin and actin-associated proteins are essential for generating molecular and morphological cell polarity, but only recently has it become accepted that microtubules can induce and/or maintain polarity. One common feature among different cell types is that microtubules can establish the position of cortical polarity, but are not required for cortical polarity per se. In this review, we discuss how different cell types utilize microtubules and microtubule-associated signaling pathways to generate cortical cell polarity, highlight common mechanisms, and discuss open questions for directing future research.