The pentose phosphate pathway (PPP), a branch of glycolysis, is crucial for the synthesis of ribonucleotides and NADPH, which are essential for fatty acid synthesis and scavenging reactive oxygen species (ROS). Cancer cells rely heavily on the PPP to meet their anabolic demands and combat oxidative stress. Recent studies have shown that neoplastic lesions have evolved to facilitate glucose flux into the PPP. This review discusses the fundamental functions of the PPP, its regulation in cancer cells, and its importance in cancer cell metabolism and survival. Key enzymes in the PPP, such as glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and transketolase (TKT), are regulated by various mechanisms, including posttranslational modifications and signaling pathways. Oncogenic proteins like p53, Ras, and mTORC1, as well as tumor suppressors like p53 and Nrf2, play significant roles in modulating the PPP. The PPP is critical for cancer cell survival and metastasis, as it generates high levels of NADPH to reduce ROS and support DNA synthesis and repair. However, the elevated PPP activity in cancer cells may also contribute to drug resistance. Targeting the PPP for cancer therapy is challenging but potentially promising, as it could disrupt the metabolic pathways that support cancer cell growth and survival.The pentose phosphate pathway (PPP), a branch of glycolysis, is crucial for the synthesis of ribonucleotides and NADPH, which are essential for fatty acid synthesis and scavenging reactive oxygen species (ROS). Cancer cells rely heavily on the PPP to meet their anabolic demands and combat oxidative stress. Recent studies have shown that neoplastic lesions have evolved to facilitate glucose flux into the PPP. This review discusses the fundamental functions of the PPP, its regulation in cancer cells, and its importance in cancer cell metabolism and survival. Key enzymes in the PPP, such as glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and transketolase (TKT), are regulated by various mechanisms, including posttranslational modifications and signaling pathways. Oncogenic proteins like p53, Ras, and mTORC1, as well as tumor suppressors like p53 and Nrf2, play significant roles in modulating the PPP. The PPP is critical for cancer cell survival and metastasis, as it generates high levels of NADPH to reduce ROS and support DNA synthesis and repair. However, the elevated PPP activity in cancer cells may also contribute to drug resistance. Targeting the PPP for cancer therapy is challenging but potentially promising, as it could disrupt the metabolic pathways that support cancer cell growth and survival.