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Laboratory investigations, whilst not essential to the diagnosis of seizures or of epilepsy, can be fundamental to determining the cause and guiding management. Over 50% of first seizures have an acute symptomatic cause, including a range of metabolic, toxic or infectious cause. The same triggers can precipitate status epilepticus, either de novo or as part of a deterioration in control in individuals with established epilepsy. Some, such as hypoglycaemia or severe hyponatraemia, can be fatal without prompt identification and treatment. Failure to identify seizures associated with recreational drug or alcohol misuse can lead to inappropriate AED treatment, as well as a missed opportunity for more appropriate intervention. In individuals with established epilepsy on treatment, some laboratory monitoring is desirable at least occasionally, in particular, in relation to bone health, as well as in situations where changes in AED clearance or metabolism are likely (extremes of age, pregnancy, comorbid disorders of renal or hepatic function). For any clinician managing people with epilepsy, awareness of the commoner derangements associated with individual AEDs is essential to guide practice. In this article, we review indications for tests on blood, urine and/or cerebrospinal fluid in patients presenting with new-onset seizures and status epilepticus and in people with established epilepsy presenting acutely or as part of planned monitoring. Important, but rare, neurometabolic and genetic disorders associated with epilepsy are also mentioned.