Unlike immunofluorescence confocal microscopy of fixed samples or microscopic surface analysis in material sciences that both involve largely indestructible samples, life-cell imaging focuses on live cells. Imaging live specimen is by definition minimally invasive imaging, and photon efficiency is the primordial concern, even before issues of spatial, temporal or, spectral resolution, of acquisition speed and image contrast come in. Beyond alerting the reader that good live-cell images are often not the crisp showcase images that you know from the front page, this chapter is concerned with providing a fresh look on one of the routine instruments in modern biological research. Irrespective of whether you are a young researcher setting up your own lab or a senior investigator choosing equipment for a new project, at some stage you will most likely face decision making on what (fluorescence) imaging set-up to buy. In as much as this choice is about a long-lived and often relatively costly piece of equipment and, more importantly, impacts on your future experimental program, this choice can be a tricky one. It involves considering a multitude of parameters, some of which are discussed here.