Adenosine monophosphate–activated protein kinase (AMPK), a metabolic protein kinase, and its upstream kinase LKB1 play crucial roles in the establishment and maintenance of cell polarity. Although the shapes of polarized cells display extraordinary diversity, the key molecules involved in cell polarity are relatively well conserved. Here, we review the mechanisms and factors responsible for organizing cell polarity and the role of LKB1 and AMPK in cell polarity.