Cancer stem cells (CSCs) represent a small population of cancer cells that are able to self-renew and initiate tumors, which undergo epigenetic, epithelial-mesenchymal, immunological, and metabolic reprogramming to adapt to the tumor microenvironment as well as survive host defense or therapeutic insults. The metabolic reprogramming that accompanies cancer onset is known to be critical for the disease pathogenesis. A coordinated dysregulation of lipid metabolism is observed in nearly all cancer types. In addition to fulfilling the basic requirements of structural lipids for membrane synthesis, lipids function importantly as signaling molecules and contribute to energy homeostasis. In this review, we summarize the current progress in the attractive research field of aberrant lipid metabolism regarding CSCs in cancer progression, which provides insights into therapeutic agents targeting CSCs based upon their modulation of lipid metabolism.