The initial formation and subsequent development of the CdS/CuInSe2 interface are studied. XPS depth-compositional data are used to identify the composition of a interfacial reacted region between the CdS and Cu-ternary layers. Angular-resolved XPS confirm the existence of this transition layer which is a mixed Cu2S–Cu2S binary. Auger transitions in the XPS spectra are used to resolve those compounds. Differences in EELS spectra as a function of CdS growth are also ascribed to the existence of the interface region. The effects of annealing on the integrity of this interface and photovoltaic performance of the device are also presented. Three distinct regimes are identified: (1) T<150 °C. Device and interface properties are stable; (2) 200<T<300 °C. Se and S interdiffusion occurs, with 50%–75% degradation in cell performance; and (3) T≳350 °C. Rapid diffusion of the Cd into the Cu-ternary takes place, destroying junction integrity and causing complete device failure.