Ab initio calculations were used to study the mechanisms of the processes of Mg–Si solid state intermixing and silicide formation. An evolutionary algorithm was used to search for MgαSi(1-α) structures with lowest formation energies, Ef; the composition parameter α was varied over the range 0–1. New structures with negative formation energies have been found for α > 0.67. Tentatively, the obtained structure Mg3Si, has been observed in experiments. Besides the minimum at α = 0.67 corresponding to Mg2Si, the dependence of Ef(α) has two positive maxima: near low and high α. This dependence indicates that certain energy barriers prevent the initiation of Mg–Si intermixing. High temperatures and abundance of both Mg and Si atoms at the interface are required for initiation of the intermixing and silicide formation processes. Practical implications of this conclusion for routine and new methods of Mg2Si growth in vacuum are analyzed. Some characteristic experimental data are explained. Rational methods of fabrication of cheap and environmentally-friendly Mg2Si and related compounds for applications in solar cells and thermoelectric devices are indicated.