PPGL refers to a heterogeneous group of rare neuroendocrine tumors arising from chromaffin cells—specialized cells that produce catecholamines, the hormones driving the body’s “fight-or-flight” response. It includes two main subtypes: pheochromocytomas, which develop in the adrenal medulla (the inner part of the adrenal glands perched atop the kidneys), and paragangliomas, which occur outside the adrenals in clusters of paraganglia along the sympathetic or parasympathetic nervous system. With an annual incidence of 2 to 8 cases per million people, PPGL is a rare condition, though its true prevalence may be higher due to underdiagnosis from non-specific symptoms. It can affect individuals of any age, but most diagnoses occur between the third and fifth decades of life. A defining feature of PPGL is its strong genetic component: up to 40% of patients carry germline mutations in genes like RET, VHL, NF1, or SDH (succinate dehydrogenase) subunits, which not only increase tumor risk but also link to other associated conditions, emphasizing the need for family screening. Symptoms are primarily driven by excess catecholamine secretion (epinephrine, norepinephrine, dopamine) in most cases. The classic triad—episodic headaches, palpitations, and profuse sweating—occurs in about half of patients, but other common signs include paroxysmal or persistent hypertension, anxiety, tremors, weight loss, and flushing. Non-secretory paragangliomas, often found in the head and neck (e.g., carotid body tumors), may remain asymptomatic until they grow large enough to cause mass effects like difficulty swallowing or voice changes. Diagnosis begins with biochemical testing: plasma free metanephrines or 24-hour urine collections for metanephrines and catecholamines are the gold standards to detect elevated levels. Once confirmed, imaging studies localize the tumor: anatomical scans (CT or MRI) of the abdomen, pelvis, chest, and head/neck first, followed by functional imaging (e.g., 123I-MIBG scintigraphy, 68Ga-DOTATATE PET) to identify metastatic spread or additional tumors. Genetic testing is recommended for nearly all patients to guide treatment and family care. Localized PPGL is curable with surgical resection, but preoperative medical preparation is critical to avoid life-threatening hemodynamic instability during surgery: alpha-blockers control hypertension, then beta-blockers (if needed) manage tachycardia. For metastatic PPGL (10–15% of cases), options include targeted therapies (tyrosine kinase inhibitors), peptide receptor radionuclide therapy (PRRT), or chemotherapy, tailored to tumor characteristics. Prognosis varies widely: localized tumors have a 5-year survival rate of over 95%, while metastatic cases range from 34% to 60%, with SDHB mutations linked to poorer outcomes. Early detection is vital to prevent complications like hypertensive crises or organ damage. Genetic counseling for patients and families is essential to identify at-risk individuals and enable proactive monitoring.