This review focuses on recent advances in our understanding of the mechanisms and regulation of water-soluble vitamins (WSV) transport in the large intestine and the pancreas, two important organs of the digestive system that have not gotten their fair share of progress until recently. WSV, a group of structurally unrelated compounds, are essential for normal cellular functions and development, and thus, for overall health and survival of the organism. Humans cannot synthesize WSV endogenoursly, rather they obtain them from exogenous sources via intestinal absorption. The intestine is exposed to two sources of WSV: a dietary source, and a bacterial source (i. e., the WSV that are generated by the large intestinal microbiota). Contribution of the latter source toward human nutrition/health has been a subject of debate, and doubt, mostly on the basis that the large intestine does not have specialized systems for efficient uptake of WSV. However, recent studies utilizing a variety of human and animal colonic preparations have clearly demonstrated that such systems do exist in the large intestine. This has provided strong support that the microbiota-generated WSV are of nutritonal value to the host, and especially to the nutritional needs of the local colonocytes and their helath. With regards to the pancreas, WSV are essential for normal metabolic activities of all its cell types, and for its exocrine and endocrine functions. Again significant progress has also been made regarding the mechanisms involved in the uptake of WSV, and the effect of chronic alcohol exposure on the uptake processes.