The immunological synapse (IS) is the junction between an immune cell (e.g., a T or NK cell) and another cell (e.g., an antigen-presenting cell (APC), or a tumor cell). The formation of the IS is crucial for cellmediated immunity, and as such, an understanding of both the composition of the IS and the factors that drive its formation are essential for understanding how and when NK cells eliminate susceptible target cells. The supported lipid bilayer (SLB) system is a highly effective tool for directly studying the IS. SLBs confer three main advantages: (1) they allow for synapse formation on a level horizontal surface, allowing for direct visualization of the IS under high resolution imaging systems, (2) they mimic the surface of a target cell by providing a fl uid mosaic into which surface proteins can be embedded while permitting free motion in two dimensions, which is important for studying the dynamics of synapse formation, and (3) they allow investigators to determine the exact composition of the bilayer, thus in turn allowing them to answer very specifi c questions about the IS. It is our hope that this chapter will furnish readers with an awareness of the applications of the SLB system for studying the IS in NK cells, and also of a basic knowledge of how to use this system for themselves.