Spent coffee grounds (SCG) and coffee silverskins (CSS) are two high-volume industrial by-products rich in valuable components, such as alkaloids, diterpenic, and phenolic compounds, triglycerides (oils), and polysaccharides. Their recovery yield and purity are highly dependent on the selected extraction method and operating conditions. This chapter discusses recent advances on the following separation technologies: solid–liquid extraction (SLE) using conventional solvents and ionic liquids, supercritical fluid extraction (SFE), subcritical water extraction, ultrasound assisted extraction, and microwave assisted extraction. SLE and SFE are the most mature approaches for the extraction of coffee by-products, although promising results have been reported for the other technologies. Solvents like ionic liquids (ILs) and deep eutectic solvents are expected to play an important role in the near future, along with other approaches, such as pervaporation, nanofiltration, sorption (adsorption and ion exchange), hydrothermal liquefaction, pulsed electric fields extraction, and products synthesis under the scope of nanotechnology. Overall, these methods produce oils/extracts rich in phenolic compounds exhibiting valuable antioxidant activity levels, with encouraging extraction yields. The optimization of both operating conditions and unit’s arrangement is crucial to ensure their technological and economic viability. Currently, a considerable number of scientific studies and patents demonstrate or claim their use for various applications, including dermatological formulations, pest control formulations, growth enhancer substrates for bacterial cultures, biodiesel production, among others.