Systemic toxicity of local anesthetics is a complex problem requiring an integrated approach to perioperative management of patients with various diseases. These guidelines describe the key aspects of this phenomenon starting with definition of basic terms and ending with description of diagnosis, treatment and emergency care for life-threatening complications. One of the most serious forms of systemic toxicity is cardiotoxicity followed by arrhythmias, impaired myocardial contractility, and even cardiac arrest. In addition, local anesthetics can cause neurotoxicity with seizures, loss of consciousness and other neurological disorders. Importantly, the risk of these complications depends on dose, administration rate and individual characteristics of patients. Regional anesthesia is effective for pain relief. However, it is also associated with certain dangers, such as inadvertent intravenous administration of local anesthetic with systemic toxicity. Early cardiopulmonary resuscitation is necessary for life-threatening complications, such as cardiac or respiratory arrest. Effectiveness of resuscitation measures largely depends on timely nature and correct technique. In case of circulatory arrest, it is recommended to use standard protocols, including chest compression, artificial respiration and defibrillation, as well as etiotropic therapy with fat emulsion as soon as possible. Fat emulsions are one of the promising methods for systemic toxicity of local anesthetics. Fat emulsions are able to bind free anesthetic molecules, reduce their concentration in blood and risk of toxic reactions. This method is particularly effective for cardiotoxic complications. Clinical guidelines contain algorithms for physicians and scales for assessing clinical status of patients. This makes it possible to optimize decision-making process and improve treatment outcomes.