Evanescent wave microscopy, also termed total internal reflection fluorescence microscopy (TIR-FM), has shed new light on important cellular processes taking place near the plasma membrane. For example, this technique can enable the direct observation of membrane fusion of synaptic vesicles and the movement of single molecules during signal transduction. There has been a recent surge in the popularity of this technique with the advent of green fluorescent protein (GFP) as a fluorescent marker and new technical developments. These technical developments and some of the latest applications of TIR-FM are the subject of this review.