Rapidly proliferating cells, including cancer cells, adapt metabolism to meet the increased energetic and biosynthetic demands of cell growth and division. Many rapidly proliferating cells exhibit increased glucose consumption and fermentation regardless of oxygen availability, a phenotype termed aerobic glycolysis or the Warburg effect in cancer. Several explanations for why cells engage in aerobic glycolysis and how it supports proliferation have been proposed, but none can fully explain all conditions and data where aerobic glycolysis is observed. Nevertheless, there is convincing evidence that the Warburg effect is important for the proliferation of many cancers, and that inhibiting either glucose uptake or fermentation can impair tumor growth. Here, we discuss what is known about metabolism associated with aerobic glycolysis and the evidence supporting various explanations for why aerobic glycolysis may be important in cancer and other contexts.