Prophylactic transient hypoxia (preconditioning) increased neuron resistance to subsequent induction of severe hypoxia. Published data and results obtained by the authors on the molecular-cellular mechanisms of hypoxic preconditioning are presented. The roles of intracellular signal transduction, genome function, stress proteins, and neuromodulatory peptides in this process are discussed. The roles of glutamatergic as well as calcium and phosphoinositide regulatory systems and neuromodulatory factors as components of "volume" signal transmission are analyzed in hypoxic preconditioning-associated induction of functional tolerance mechanisms against the acute harmful effects of hypoxia on neurons in olfactory slices.