A better understanding of the molecular mechanisms of receptor–receptor interactions is essential to comprehend the functional meaning of the phenomenon of G protein-coupled receptor (GPCR) oligomerization. In this chapter we discuss how new methodological strategies derived from non-invasive fluorescence- and luminescence-based approaches (i.e. FRET, BRET, BiFC/BiLC) have been successfully used in the study of GPCR oligomerization and consequently provided new insights into the occurrence of GPCR oligomers in living cells. These technologies alone, or in concert with complimentary methods (i.e. SRET, BRET/BiFC and SNAP-tag/TR-FRET), can be extremely powerful approaches for visualizing receptor–receptor interactions—even between more than two proteins and also in native tissues. Here we provide a thorough assessment on all biotechnological aspects of these fluorescence/luminescence-based methodologies, including the strengths and weaknesses, when applied in the study of GPCR oligomerization.