Introduction: One of the most distinctive hallmarks of cancer cells is increased glucose consumption for aerobic glycolysis, which is called the Warburg effect. In recent decades, extensive research has been carried out to exploit this famous phenomenon, trying to detect promising targetable vulnerabilities in altered metabolism to fight cancer. Targeting aberrant glucose metabolism can perturb cancer malignant proliferation and even induce programmed cell death. Areas covered: This review covered the recent patents which focused on targeting key glycolytic enzymes, including hexokinase, pyruvate dehydrogenase kinases, and lactate dehydrogenase for cancer treatment. Expert opinion: Compared with the conventional cancer treatment, specifically targeting the well-known Achilles heel, the Warburg effect has attracted considerable attention. Although there is still no single glycolytic agent for clinical cancer treatment, the combination of glycolytic inhibitor with conventional anticancer drugs or the combined use of multiple glycolytic inhibitors are being investigated extensively in recent years, which could emerge as attractive anticancer strategies.