Although they were identified as long ago as the 1960s, there are still many unknowns regarding the functions and composition of membrane contact sites between the endoplasmic reticulum (ER) and the trans-Golgi (TG). While it seems to be fairly well established that they facilitate lipid exchange between the two organelles, much less is known about how they are regulated. A bottleneck in the study of the ER-TG contact sites has been the absence of methods for their biochemical isolation and visualization by light microscopy. Herein we provide an overview of current knowledge about ER-TG contact sites with a particular emphasis on the questions that remain to be explored.