Eukaryotic cells contain a number of different membrane compartments that have specialized roles. Each compartment depends on a specific mixture of proteins for its identity and function. For many compartments, proteins arrive by way of small membrane vesicles that travel through the cell from an originating compartment (Bonifacino and Glick, 2004; Gürkan et al., 2007). Small membrane vesicles are created by the action of coat proteins that deform membranes into the shape of vesicles and simultaneously select ‘cargo’proteins for inclusion into these vesicles (Kirchhausen, 2000; Bonifacino and Lippincott-Schwartz, 2003). Coat protein complex II (COPII) is a set of highly conserved proteins that is responsible for creating small membrane vesicles that originate from the endoplasmic reticulum (ER)(Lee et al., 2004; Barlowe et al., 1994). The formation and movement of these COPII-derived vesicles is a crucial first step in the cellular secretion pathway, through which membrane and lumenal cargo proteins are transported from their site of synthesis at the ER on to other membrane compartments in the cell. In this Cell Science at a Glance article, we first consider the five proteins that constitute the conserved core of the COPII vesicle creation machinery and take a look at how they are able to shape membranes, select cargo proteins that need to be transported, and form a polymeric coat that results in a vesicle. Then, we examine more recent discoveries that show how deficiencies in COPII can lead to disease. Finally, we briefly explore how additional factors can work with the COPII proteins to enhance transport efficiency in particular cases. Together with the accompanying poster, we hope that this brief overview will be useful and encourage readers to consider how efficient or deficient forward transport can affect the activity of the proteins they study.