The exploitation of low‐affinity molecular interactions in protein labeling is an emerging topic in optical microscopy. Such non‐covalent and low‐affinity interactions can be realized with various concepts from chemistry and for different molecule classes, and lead to a constant renewal of fluorescence signals at target sites. Further benefits are a versatile use across microscopy methods, in 3D, live and many‐target applications. In recent years, several classes of low‐affinity labels were developed and a variety of powerful applications demonstrated. Still, this research field is underdeveloped, while the potential is huge.