A retrospective review of sedation of lizards using dexmedetomidine-midazolam (DM) with or without ketamine administered intramuscularly or subcutaneously was performed. Forty-four sedation events, involving 25 individuals and 16 different species of lizards, were reviewed. Sedation was performed for physical examinations, imaging, biopsy collection, and wound treatments. Dexmedetomidine (median: 0.08 mg/kg, 25–75%: 0.05–0.1 mg/kg, range: 0.03–0.3 mg/kg) combined with midazolam (median: 1 mg/kg, 25–75%: 0.85–1 mg/kg, range: 0.5–2 mg/kg) was used in 11/44 (25%) sedation events. In 33/44 (75%) sedation events, ketamine (median: 2.9 mg/kg, 25–75%: 2.43–3 mg/kg range: 0.9–5 mg/kg) was administered in addition to DM. Insufficient depth of sedation was reported for 2/44 (4.5%) events. Atipamezole (10 times the milligrams dose of dexmedetomidine) and flumazenil (median: 0.05 mg/kg, 25–75%: 0.05–0.05 mg/kg, range: 0.01–0.1 mg/kg) were administered for reversal of the sedative effects of DM in all sedation events. The most common complication noted was apnea, which occurred in 2/44 (4.5%) sedation events and resolved following administration of the reversal agents.