The plasma membrane is a two-dimensional compartment that relays most biolo
gical signals sent or received by a cell. Signalling involves membrane rece
ptors and their associated enzyme cascades as well as organelles such as ex
ocytic and endocytic vesicles. Advances in light microscope design, new org
anelle-specific vital stains and fluorescent proteins have renewed the inte
rest in evanescent field fluorescence microscopy, a method uniquely suited
to image the plasma membrane with its associated organelles and macromolecu
les in living cells. The method shows even the smallest vesicles made by ce
lls, and can image the dynamics of single protein molecules.