Pheochromocytoma (PHEO) and paraganglioma (PGL) are tumors with strong genetic determinism: germline mutations in susceptibility genes are detected in 40% of subjects, with mutation frequency of 10–12% also in patients with sporadic presentation. Many susceptibility gene have been discovered and genetic screening should be proposed to all subjects with PHEO and PGL (PPGL). Genetic analysis is currently performed through next generation sequencing technologies, which allows for the simultaneous study of many genes, overcoming the difficulties associated with the study of diseases with high genetic heterogeneity. PPGL susceptibility genes include “old genes” associated with neurofibromatosis type 1 (NF1 gene), Von Hippel Lindau syndrome (VHL gene) and multiple endocrine neoplasia type 2 syndrome (RET gene), the family of SDHx genes (SDHA, SDHB, SDHC, SDHD, SDHAF2), which are responsible for more than half of hereditary PPGL, and the less frequently involved TMEM, MAX, and FH genes. Mutations in different genes express a peculiar phenotype: the identification of a pathologic variant in susceptibility genes makes it possible to propose to the patient a tailored surveillance program according to the risk of relapse, malignancy, and involvement of other organs, and also allows extension of genetic analysis to relatives and implementation of presymptomatic surveillance in mutation carriers.