The success of experimental studies and failure of clinical trials of neuroprotective drugs proposed for the treatment of ischemic stroke determines the need for an analysis of existing models. Protocols of most laboratory models of stroke include general anesthesia. Inhalation and intravenous anesthetics affect the signaling pathways involved in the neuroprotective and neurotoxic mechanisms. Activation of ionotropic glutamatergic AMPA- and NMDA-receptors in the ischemic brain tissue is accompanied by necrosis and apoptosis of neurons. Certain anesthetics influence the activity of AMPA-receptors, including the phosphorylation and internalization/externalization of GluR-receptor subunits. Besides direct blockade of NMDA receptors several anesthetics affect expression and phosphorylation of NMDA receptor NR1 subunit. The mechanism of action of many inhalation and intravenous anesthetics is associated with activation of ionotropic GABA A receptors; this increases resistance of cells to excitotoxicity and reduces ischemic neuronal damage. In addition to the ionotropic receptors several anesthetics act through metabotropic transmembrane G-protein-coupled receptors. Anesthetic indirectly influence metabotropic GABA B and glutamate mGlureceptor by regulating protein-protein interactions and phosphorylation of receptor subunits. Some inhalation and intravenous anesthetics activate adenosine A1-receptor, increasing the concentration of extracellular adenosine. Anesthetic preconditioning may be accompanied by long-term neuroprotection coupled to activation of p38 MAPK, and mTOR and CREB transcription factors. A possible solution to the problem of the influence of anesthetics on the results of laboratory studies would be the use of parallel-group comparison of different general anesthetics. The effects of general anesthetics determine the need of studies of their neuroprotective potential in terms of ischemic stroke.