This paper accumulates the recent advances in scientific understanding of the problem of seismo-ionospheric coupling. Present research focuses on three main areas: the physical mechanism, main phenomenological features of ionospheric variations associated with earthquakes, and their statistical properties permitting use of them in practical applications. In this paper, the developed physical model bridges the traditional precursors of earthquakes and ionospheric ones, demonstrating that the latter belong to the same family. In this regard the earthquake preparation zone is key generating the scaling law and the relationship between geochemical precursors, anomalous electric field involved in ionospheric variations initiated, and the ionospheric irregularities themselves. Revealed ionospheric precursor phenomena and their statistical parameters are used to develop a pattern recognition technique and other statistical processing techniques that can be used in short-term earthquake prediction. Finally a possible system of ground based measurements and satellite monitoring is proposed for regional and global monitoring and possible short-term prediction of destructive earthquakes.