Combining single-molecule manipulation and single-molecule detection

•Here we review recent developments in combining single molecule force-fluorescence techniques.•We discuss combinations with optical trapping, magnetic trapping, and atomic force microscopy.•Recent development of fluorescence based force sensors provides a new tool for measuring forces in vivo. Single molecule force manipulation combined with fluorescence techniques offers much promise in revealing mechanistic details of biomolecular machinery. Here, we review force-fluorescence microscopy, which combines the best features of manipulation and detection techniques. Three of the mainstay manipulation methods (optical traps, magnetic traps and atomic force microscopy) are discussed with respect to milestones in combination developments, in addition to highlight recent contributions to the field. An overview of additional strategies is discussed, including fluorescence based force sensors for force measurement in vivo. Armed with recent exciting demonstrations of this technology, the field of combined single-molecule manipulation and single-molecule detection is poised to provide unprecedented views of molecular machinery.