Secondary intermediaries, or secondary messengers, are intracellular signaling molecules released in response to stimulation of receptors. They are the initiating elements in many intracellular signaling cascades and cause the activation of primary effector messenger proteins. This triggers a cascade of physiological changes that are important for the growth, development, differentiation of cells, gene transcription, protein biosynthesis, secretion of hormones, neurotransmitters or cytokines, changes in bioelectric activity and cell migration, and apoptosis induction. Several universal secondary signaling systems exist in the cell, which are mediated by the main three types of mediators: hydrophobic molecules: water-insoluble molecules (diacylglycerol, phosphatidylinositol) that bind to cell membranes and diffuse across intermembrane spaces to organelle membranes, reaching and acting with membrane-bound secondary effector proteins; hydrophilic molecules: water-soluble molecules (cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), inositol triphosphate, calcium), which are distributed in the aqueous medium of the cytoplasm; gases: nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), which pass through the cell membrane and diffuse into the cytoplasm. The purpose of this review is to generalize and systematize literature data on the mechanisms for the implementation of the functions of secondary messengers in the intercellular signaling system. The study of their functioning and regulation can serve as a fundamental basis for the study of normal brain and experimental pathology, creating the basis for subsequent clinical studies. Keywords: Secondary Mediators; Intercellular Signaling; Effector Proteins; Receptors; Ligands; Brain.