The article by Stefan W. Hell discusses the principles and advancements in far-field optical microscopy, particularly focusing on the development of nanoscopy techniques that overcome the diffraction limit. Traditional lens-based microscopes have been limited to resolving objects no smaller than about half the wavelength of light due to diffraction. However, in the early 1990s, new physical concepts emerged that allowed for the creation of fluorescence microscopes with nanoscale spatial resolution. Hell outlines several key methods, including stimulated emission depletion (STED) microscopy, ground-state depletion (GSD), saturated pattern excitation microscopy (SPEM), and stochastic optical reconstruction microscopy (STORM). These techniques achieve sub-diffraction limit resolution by switching fluorescent molecules on and off sequentially in time, allowing for the visualization of objects closer than 200 nm apart. The article explains the underlying principles of these methods, emphasizing the importance of switching between different states of fluorescent molecules, such as between a fluorescent state and a dark state. The switching mechanisms and the intensities required for these transitions are crucial for achieving high-resolution imaging. For example, STED microscopy uses a doughnut-shaped beam to switch molecules off, while GSD uses a metastable triplet state to confine molecules in a small spatial region. Hell also discusses the differences between targeted and stochastic switching methods. Targeted switching involves using spatial light intensity distributions to define the coordinates where molecules are switched on or off, while stochastic switching relies on random switching of individual molecules. Each method has its advantages and limitations, with targeted switching being faster but requiring more complex optics, and stochastic switching being more sensitive and suitable for parallelized detection. The article concludes by discussing future developments, such as the use of multiple distinguishable bright states and the potential for even higher resolution with advanced molecular switches. Hell emphasizes that the key to nanoscale resolution lies in the ability to switch between different states of fluorescent molecules, rather than in the wave nature of light or the limitations of conventional lenses.The article by Stefan W. Hell discusses the principles and advancements in far-field optical microscopy, particularly focusing on the development of nanoscopy techniques that overcome the diffraction limit. Traditional lens-based microscopes have been limited to resolving objects no smaller than about half the wavelength of light due to diffraction. However, in the early 1990s, new physical concepts emerged that allowed for the creation of fluorescence microscopes with nanoscale spatial resolution. Hell outlines several key methods, including stimulated emission depletion (STED) microscopy, ground-state depletion (GSD), saturated pattern excitation microscopy (SPEM), and stochastic optical reconstruction microscopy (STORM). These techniques achieve sub-diffraction limit resolution by switching fluorescent molecules on and off sequentially in time, allowing for the visualization of objects closer than 200 nm apart. The article explains the underlying principles of these methods, emphasizing the importance of switching between different states of fluorescent molecules, such as between a fluorescent state and a dark state. The switching mechanisms and the intensities required for these transitions are crucial for achieving high-resolution imaging. For example, STED microscopy uses a doughnut-shaped beam to switch molecules off, while GSD uses a metastable triplet state to confine molecules in a small spatial region. Hell also discusses the differences between targeted and stochastic switching methods. Targeted switching involves using spatial light intensity distributions to define the coordinates where molecules are switched on or off, while stochastic switching relies on random switching of individual molecules. Each method has its advantages and limitations, with targeted switching being faster but requiring more complex optics, and stochastic switching being more sensitive and suitable for parallelized detection. The article concludes by discussing future developments, such as the use of multiple distinguishable bright states and the potential for even higher resolution with advanced molecular switches. Hell emphasizes that the key to nanoscale resolution lies in the ability to switch between different states of fluorescent molecules, rather than in the wave nature of light or the limitations of conventional lenses.