The sphingolipid metabolic network generates a large and extremely diverse family of lipids with distinct and sometimes opposing biologic functions. When levels of particular sphingolipid species are significantly altered or inappropriately expressed, human disease often results. A major challenge in the field is to understand the mechanisms orchestrating the metabolic network to allow the production of specific sphingolipids with proper quantity, timing and location and without the aberrant expression of other interconnected sphingolipids that may be detrimental. I will discuss mechanisms that orchestrate the sphingolipid metabolic network to enable precise expression of its unique biologic functions and their significance in mammals.