We need to look beyond our gut instincts to use information on "simple" intestinal physiological parameters as they have been presented to us in the past. Here we present a discussion on such parameters, old and new, and ask how much we really understand them. Behaviour of drugs and delivery systems in the intestine depends on many physiological factors including fluid volume, fluid composition, transit, motility, bacteria and pH, which are further influenced by food, gender and age. These are often considered well understood, but their true variability and idiosyncrasies are not fully appreciated or utilised in intestinal dosage form design or in vitro testing. There are still many unknowns in these areas. The distal gut especially has been neglected, and the influence of disease is often ignored. As pharmaceutics moves forward into the molecular era an understanding of the role of cellular mechanisms of transporters and metabolic enzymes is important, but the basics must not be forgotten. This discussion on intestinal physiology is utilised to address those areas which require further research and understanding, and new technologies are highlighted. Better understanding of the fundamental information available can open new avenues for research and pave the way for the future of gastrointestinal drug delivery.