A physico-chemical consideration of the interfacial interaction and diffusion resulting in the formation of chemical compound layers at the interface of initial substances A and B is presented. The layer-growth kinetics is shown to be much more complicated than it follows from conventional diffusional views neglecting interfacial reactions. In the majority of multiphase binary systems, layer occurrence appears to be sequential rather than simultaneous. Under conditions of diffusion control, the number of simultaneously growing compound layers at the A–B interface cannot exceed two. Multiple layers (three and more) can only form as a result of secondary processes connected with the rupture of a diffusion couple. In such cases, great care is necessary when calculating diffusion coefficients to avoid obtaining their physically meaningless values.