Background: Despite the increasing numbers of obese patients undergoing elective surgery, there is a lack of evidence-based dosing guidelines for peri-operative medications in obesity. Objective: The objective was to systematically review the dosing and outcomes of peri-operative medications used in obese elective surgical patients. Methods: Medical subject headings and general keywords were used to systematically search multiple databases (PubMed, EMBASE, Cochrane Library and CINAHL). Studies of medications in obese surgical patients were included if they had a non-obese control or comparative dosing scalar group. The National Health and Medical Research Council GRADE tool was used to assess quality of evidence for each drug. Results: Thirty-three studies of six drug classes were identified: anaesthetics (n = 6), muscle relaxants (n = 10), neuromuscular reversal agents (n = 3), analgesics (n = 2), antibiotics (n = 5) and anticoagulants (n = 7). A variety of dose scalars and/or recommendations was observed for various medications. Lean body weight was proposed as a suitable weight scalar for induction of anaesthesia with propofol whereas total body weight for maintenance of anaesthesia with propofol and depolarizing muscle relaxants. Ideal body weight was reported as an appropriate dosing scalar for non-depolarizing muscle relaxants and neuromuscular reversal agents. Both corrected body weight 40% and ideal body weight were reported as suitable weight scalars for post-operative analgesia with morphine. The standard 2-g dose of cefazolin appeared effective in the prevention of surgical site infection. Body mass index stratified dosing of enoxaparin was effective for venous thromboembolism prevention. Conclusion: No drug recommendation achieved an “Excellent” quality of evidence. Limited data suggest that clinicians should consider each individual class of medication when selecting a dose for obese surgical patients. Routine use of fixed-dosing regimens is likely to under- or overdose obese patients thus predisposing them to adverse drug events or treatment failure leading to patient harm.