Protein-protein interactions play a central role in numerous processes in the cell. Given the complex organization of cell, it is very likely that the molecular behavior of proteins in a test tube is different from that in living cells. For this reason, the conventional approaches used to study protein-protein interactions, including two-hybrid yeast assay, immunoprecipitation assay, etc, may not represent the physiological nature in living cells. Fluorescence resonance energy transfer (FRET) is a recently developed laser technique, which offers a unique opportunity to monitor real-time protein-protein interactions or protein conformational changes within a living cell and to follow the time course of the changes in FRET corresponding to cellular events. The observation of such dynamic molecular events in its natural environment provides vital insight into the protein-protein interactions within the cell. The applications of this approach to study the protein-protein interactions in vivo are briefly reviewed.