It is worth remembering that the first optical detection of single molecules arose out of an industrial research lab in the late 1980’s, while exploring the fundamentals of molecular frequency domain optical storage at low temperatures. This work led to the observations of blinking and optical switching, key concepts that provide the foundations of super-resolution imaging with single molecules. Super-resolution microscopy has opened up a new frontier in which biological structures and behavior can be observed in fixed and live cells with resolutions down to 20-40 nm and below, and many examples abound. Current methods development research addresses ways to image in thick cells and to extract more information from each single molecule such as 3D position and orientation, as well as to assure not only precision, but also accuracy. Further, new labels are needed which provide more photons before photobleaching. At the same time, it is worth noting that in spite of all the current focus on super-resolution, even in the “conventional” low concentration, single-molecule tracking regime where the motions of individual biomolecules are recorded rather than the shapes of extended structures, much can be learned about dynamic biological processes when ensemble averaging is removed. Beyond tracking, trapping of single molecules in solution for extended measurement of multiple variables is a powerful way to examine photodynamics of photosynthetic antenna proteins and other biomolecules.