The stability of the CdS/CuInSe2 (CIS) heterojunction is critical to understanding the projected lifetime of CIS devices and the effect of processing conditions on the nanoscale chemistry of the heterojunction. This article reports the results of annealing heterojunctions between CdS deposited by chemical bath deposition and single crystal and polycrystalline CIS films between 200 and 500 °C for 10 to 150 min. No atomic movement was observed by secondary ion mass spectrometry at temperatures of 300 °C and below. At 400 °C even for the shortest time studied, Cu and In were found throughout the region initially consisting of CdS only and Cd was found to have moved into the CIS. In the polycrystal, annealing at 500 °C resulted in movement of Cd throughout the CIS layer. No time dependence was observed in the 400 and 500 °C anneals indicating that a reaction had occurred forming a compound that was in thermodynamic equilibrium with the remaining CIS. Diffusion turns on rapidly between 300 and 400 °C, indicating a high activation energy for atomic movement (∼2.4 eV). The onset of diffusion is consistent with the onset of Cu diffusion in CIS.