The list of drugs patients may be exposed to during the perioperative and postoperative periods is potentially extensive. It includes induction agents, neuromuscular blocking drugs (NMBDs), opioids, antibiotics, sugammadex, colloids, local anesthetics, polypeptides, antifibrinolytic agents, heparin and related anticoagulants, blue dyes, chlorhexidine, and a range of other agents depending on several factors related to individual patients’ clinical condition and progress in the postoperative recovery period. To avoid poor or ultrarapid metabolizers to a particular drug (for example tramadol and codeine) or possible adverse drug reactions (ADRs), some drugs may need to be avoided during or after surgery. This will be the case for patients with a history of anaphylaxis or other adverse events/intolerances to a known drug. Other drugs may be ceased for a period before surgery, e.g., anticoagulants that increase the chance of bleeding; diuretics for patients with acute renal failure; antihypertensives relative to kidney injury after major vascular surgery; and serotonergic drugs that together with some opioids may rarely induce serotonin toxicity. Studies of germline variations shown by genotyping and phenotyping to identify a predisposition of genetic factors to ADRs offer an increasingly important approach to individualize drug therapy. Studies of associations of human leukocyte antigen (HLA) genes with some serious delayed immune-mediated reactions are ongoing and variations of drug-metabolizing cytochrome CYP450 enzymes, P-glycoprotein, and catechol-O-methyltransferase show promise for the assessment of ADRs and non-responses to drugs, particularly opioids and other analgesics. Surveys of ADRs from an increasing number of institutions often cover small numbers of patients, are retrospective in nature, fail to clearly identify culprit drugs, and do not adequately distinguish immune-mediated from non-immune-mediated anaphylactoid reactions. From the many surveys undertaken, the large list of agents identified during and after anesthesia and surgery are examined for their ADR involvement. Drugs are classified into those most often involved, (NMBD and antibiotics); drugs that are becoming more frequently implicated, namely antibiotics (particularly teicoplanin), and blue dyes; those becoming less frequently involved; and drugs more rarely involved in perioperative, and postoperative adverse reactions but still important and necessary to keep in mind for the occasional potential sensitive patient. Clinicians should be aware of the similarities between drug-induced true allergic type I IgE/FcεRI- and pseudoallergic MRGPRX2-mediated ADRs, the clinical features of each, and their distinguishing characteristics. Procedures for identifying MRGPRX2 agonists and diagnosing and distinguishing pseudoallergic from allergic reaction mechanisms are discussed.Graphical Abstract