The buccal mucosa offers excellent possibilities for the (long-term) delivery of suitable drugs, especially for metabolically unstable drugs, such as peptides. A review is given of the present knowledge about buccal drug absorption and drug delivery devices. The structure and physiology of the oral mucosae are described, as well as interspecies differences with respect to tissue permeability. Methods to determine mucosal drug absorption, either in vivo or in vitro, are discussed, as well as absorption pathways, mechanisms, and enhancement. Technological strategies to control transbuccal drug absorption comprise the design of mucoadhesive devices in order to shorten diffusion pathways and prolong administration, and structural and chemical modulation of the device with the aim of shifting the rate-limiting transport step from the tissue to the device. Finally, examples of buccally administered drugs are given and devices currently used in local therapy are described.