Since NK cells specialize in contact-dependent functions including cytotoxicity, interest has focused on the direct study of the interface between the NK cell and the cell with which it is interacting. This interface is also known as the immunological synapse and is characterized by an extraordinary number of dynamic molecular events that have the potential to result in NK cell function. Here we describe microscopy-based methods for evaluating and quantifying the NK cell immunological synapse that can be useful in enabling experimental studies.