Int. J. Environ. Res. Public Health 2010, 7 943 The majority of mechanisms proposed thus far to explain bioregulatory function of extremely weak magnetic fields can be assigned to one of three groups: (1) Mechanisms following the “plasma membrane hypothesis”, which proposes that the cell membrane is a primary biological receiver of magnetic signals, in that it responds to magnetic field influences by changes of its potential, and modulates the distribution and activity of integral membrane proteins and ion channels (e.g., Ca2+ channels). However, the primary molecular interaction remains unclear. (2) Free radical mechanisms. The basis of these mechanisms is the phenomenon that magnetic fields can increase the lifetime of free radicals, i.e., stabilize them for longer. This results in an increase in free radical concentration in cell compartments, and hence biological changes including activation of signaling cascades (reviewed in [33]). (3) The ion resonance model, which implicates the combined action of the ELF MF and a weak static magnetic field (for example - geomagnetic field) [37,38]. In describing possible roles of the electron paramagnetic resonance in mechanisms of biological responses to EMF exposure, Fursa has concluded that “Electrons and nuclei, which possess magnetic moment, are the “magnetic antennae” in any biosystem, including human beings. They are able to receive and radiate electromagnetic energy selectively depending of the field’s frequency (ν) and gyromagnetic ratio (γ)” [34]. In our view, most genetic and other bioregulatory effects of weak magnetic fields (including geomagnetic field) can be achieved via the pair-radical mechanism of biological magnetoreception, first proposed by Schulten and coauthors [39]. Therefore, our main goals are to analyze the pair-radical mechanism, to propose and substantiate an expanded version of signaling pathways it can operate, and to outline corresponding medical-biological implications. 3.1. Radical Pairs and Pair Radical Reactions Radicals are very reactive paramagnetic chemical species because they have an odd number of electrons and consequently unpaired electron spins that may be found in one of two spin states, designated ↑ or ↓. To create radicals usually requires the input of external energy. Electron excitation by light is the main route to create radicals. When they are formed from diamagnetic precursors, radicals are created in pairs. A pair of radicals generated from the same diamagnetic precursor is called a geminate radical pair (G-pair). The radical pair is a short-lived reaction intermediate. Two radicals formed in tandem may have their unpaired electron spins either antiparallel (↑↓, a singlet state—S, with zero total electron spin) or parallel (↑↑, a triplet state—T, with unit spin). The radical pairs have unique properties. Since each electron spin has an associated magnetic moment, the interconversion and chemical fates of the S and T states can be influenced by internal and external magnetic fields (Figure 3). The minimum requirement for a radical pair reaction to be sensitive to an external magnetic field is that at least one of the S and T states undergoes a reaction that is not open to the other, usually as a consequence of the requirement to conserve spin angular momentum [40].