Considerable advances over the past two decades in biochemical testing and clinical genetics of phaeochromocytoma and paraganglioma underly emerging needs to integrate the two disciplines in order to improve diagnosis and management of affected patients. Laboratory testing most usually follows clinical suspicion based on signs and symptoms of presumed catecholamine excess or a finding of an incidentaloma, though is increasingly carried out in patients due to hereditary risk associated with mutations of upwards of 15 genes. These and various somatic pathogenic gene variants result in distinct catecholamine-related biochemical presentations that should be considered when interpreting laboratory results or selecting an appropriate test. For this, advances in understanding catecholamine metabolism have clarified why measurements of the O-methylated catecholamine metabolites rather than the catecholamines themselves or other metabolites are important for effective diagnosis. The critical metabolites, normetanephrine and metanephrine, produced respectively from noradrenaline and adrenaline, can be measured in plasma or urine. For patients with signs and symptoms of catecholamine excess, either test will invariably establish the diagnosis, whereas the plasma test provides higher sensitivity for patients screened due to an incidentaloma or a hereditary predisposition. Additional measurements of plasma methoxytyramine can be important for some tumours, such as paragangliomas and for surveillance of patients with certain gene mutations or who are at risk of metastatic disease. Avoidance of false-positive test results is best achieved by plasma measurements with appropriate reference intervals and attention to preanalytics, including sampling blood in the fully supine position. Follow-up of positive results, including optimisation of preanalytics for repeat tests or whether to proceed directly to anatomic imaging or confirmatory clonidine tests, depends on the nature of test results, which can also suggest likely size, adrenal versus extra-adrenal location, metastatic involvement or even underlying mutations of tumour susceptibility genes. For the latter application, information from catecholamine and energy pathway metabolomes can be used not only to point to the most likely mutated genes but also to establish pathogenic functionality of new variants. Modern biochemical testing now makes diagnosis of PPGL relatively simple and is also meeting needs for integration with genetic testing for improved diagnosis and management of patients with the tumours.