Ruminants have a specialised digestive system that contains anaerobic bacteria and protozoa capable of digesting the cellulosic materials that are so common in plant materials. In addition, their distinct digestive system can change the metabolism and mode of action of some nutrients, medicines or other bioactive materials when delivered orally or may provide opportunities for alternative oral dosing strategies. In particular, there is interest in administering a relatively large depot of some drugs into the rumen, which then provides for a prolonged and sustained release of small quantities of these drugs over time. Any strategy to develop a new ruminal drug delivery system must take into account the characteristics of the digestive system of ruminants and its specific bioactive application. For example, in the case of products to control parasitic infections, the development of the host's immunity against the nematodes, which can be acquired during the pasture season, must be considered; likewise, where pharmacologically active materials are used to manipulate a particular metabolic or biochemical process, one must always be aware of interactions with other processes, which might eventuate. This article reviews the necessary concepts, the issues and the challenges to construct ruminal drug delivery systems.