Diatoms are unique microalgae that possess highly structured skeletons composed of silica and offer very promising and diverse applications. This chapter addresses the domains in which they could be applied: monitoring of water quality, paleoclimatic studies, production of biofuels, pharmaceuticals, nanotechnology, and aquaculture. They have been used as bioindicators in the assessment of water quality, while fossils of diatoms in sediment cores reveal past climates. Some species of diatoms containing high amounts of lipids are potential candidates for the production of biofuel. They are used in pharmaceuticals for contributing to drug delivery systems, in nanotechnology applications where skeletons of diatom silica are used, and in aquaculture, they are the natural food source for aquatic larvae. Other versatile applications include use in pesticides, toothpaste abrasives, filtering media in many industries, from industry to cosmetics, waste water treatment, clean-up of oil spills, and climate change researches. This chapter provides a comprehensive overview on diatom applications and points out their significance in the environmental, industrial, and scientific domains.