Cellular oxygen sensing and coordination of an adequate response towards hypoxia are essential for surviving of organisms exposed to variations in oxygen supply. The transcription factors complex hypoxia inducible factor-1 (HIF-1) as the master regulator of cellular O2 homeostasis is formed by an O2-sensitive a- and a constitutive b-subunit (ARNT). Regulation of the assembly and the activity of this complex are key events in cellular O2-sensing. Modern confocal microscopy provides techniques like fluorescence resonance energy transfer (FRET) to study protein-protein interactions involved in this sensing pathway in living cells. The mobility and diffusion characteristics of HIF-1a and ARNT inside living cells can be investigated by the fluorescence recovery after photobleaching technique (FRAP). By 2-photon microscopy we have analysed the 3D structure of the HIF-1 complex using fusion proteins of partners of the HIF-1 complex and fluorescent protein assembly of the complex. Our results provide an insight into the protein-protein interaction and protein movement processes inside living cells under hypoxic conditions.