Whispering gallery mode (WGM) microresonators, thanks to their unique properties, have allowed researchers to achieve important results in both fundamental research and engineering applications. Among the various geometries, microspheres are the simplest 3D WGM resonators; the total optical loss in such resonators can be extremely low, and the resulting extraordinarily high Q values of 108–109 lead to high energy density, narrow resonant-wavelength lines and a lengthy cavity ringdown. They can also be coated in order to better control their properties or to increase their functionality. Their very high sensitivity to changes in the surrounding medium has been exploited for several sensing applications: protein adsorption, trace gas detection, impurity detection in liquids, structural health monitoring of composite materials, detection of electric fields, pressure sensing, and so on. In the present paper, after a general introduction to WGM resonators, attention is focused on spherical microresonators, either in bulk or in bubble format, to their fabrication, characterization and functionalization. The state of the art in the area of biosensing is presented, and the perspectives of further developments are discussed.