Fluorescence methods based on the resonance energy transfer phenomenon are currently extensively used to study biological processes, particularly interactions of G-protein coupled receptors. The development of molecular engineering has made it feasible to produce fluorescently tagged fusion proteins, which constitute a model system for studies of receptors oligomerization. It is widely accepted, that physical interactions between receptors might be of great importance for development of potential therapeutic factors, which influence signal transduction across the membrane. Here, we report on a variety of fluorescence approaches commonly used to investigate receptors oligomerization. Comparative studies reveal that even a relatively simple method, such as steady-state fluorescence spectroscopy could be useful in verifying receptor interactions. However, more sophisticated techniques as confocal microscopy and fluorescence lifetime microscopy not only provide quantifiable data of high relevance but also allow observations of dynamic processes in complex biological systems.