Capsicum peppers have been recognised as useful plants throughout human history. Long before humans were able to understand why the species was beneficial, Capsicum fruits were already being consumed, not only as a spice, but as medicinal ingredients. Capsicum was traditionally used as a local anaesthetic, for the treatment of stomach and respiratory disorders, to heal wounds, and to prevent infection and inflammation. The unique pharmacological applications of peppers are mainly related to the interaction of capsaicinoids with TRPV1, a vanilloid nociceptor that can trigger a response to pain and heat. This interaction is also responsible for the characteristic pungency of peppers. In addition to the biological properties of Capsicum directly related to TRPV1 (e.g. analgesic and anti-inflammatory actions), other chemical compounds present in this species, such as phenolic acids and flavonoids, enable Capsicum species to be used as antioxidant, antiviral and anticarcinogenic agents. This chapter reviews the remarkable pharmacological properties of Capsicum and the mechanisms behind them.