In the present chapter a wide view of the use of supercritical fluids applied to Natural Product Extraction will be given. Supercritical Fluid Extraction (SFE), especially using CO2, can be a very interesting alternative to classical extraction methods for two main reasons: tunability and sustainability. In the first part of the chapter the fundamentals of SFE as well as the basic equipment and how certain parameters affect the extraction process in order to optimize it are outlined. Besides, the use of Gas Expanded Liquids using supercritical fluids is explored in the field of natural product extraction. The second part of this chapter is focused on applications of supercritical fluids for extraction from different sources: plants, marine products (algae, microalgae and others), and agricultural and food by-products. Also, a case study of a “Compressed fluids biorefinery platform” is shown using three sequential extractions, each one using the residue from the previous extraction step, and different types of products were obtained (lipids, carotenoids, antioxidants, and protein-carbohydrates).