Mild therapeutic hypothermia (MTH) has improved neurological outcome of comatose patients after cardiac arrest (CA). Since the first clinical studies performed in this setting, sedation has always been associated with cooling procedures. The use of sedative drugs during MTH is required because it allows faster achievement and better maintenance of target temperature. Further studies are necessary to prove any potential neuroprotective effects of sedation after CA. No differences in clinical outcomes have been found among different drugs, except for those related to their intrinsic pharmacological properties: the association propofol/remifentanil provides a faster recovery of consciousness than midazolam/fentanyl but is associated with the need of more vasopressors to maintain stable hemodynamic. Moreover, pharmacokinetic properties of these drugs are often altered during MTH so that standard drug regimens could result in overdosing because of reduced clearance. Neuromonitoring could be helpful to titrate drugs' effects and detect earlier complications (i.e. seizure), while a wake-up test should be avoided during the first 24 hours after CA.