Over a period of 15 years the concept of G protein-coupled receptor (GPCR) dimerization moved from a challenging hypothesis to a scientific fact, which is now accepted by the vast majority of the scientists working in the field. However, several important issues remain debated such as the biological function of dimerization, or the actual complexity of the oligomeric organization. Because of its major potential implications in physiology and pharmacology, the question of GPCR heterodimerization (or hetero-oligomerization) is currently one of the most central. Several complementary experimental approaches are used to investigate these novel important aspects of GPCR biology. In this context, Bioluminescence Resonance Energy Transfer-based techniques are extremely powerful, provided that they are conducted with the appropriate (numerous) controls and correctly interpreted.