Initiation and progression of immune responses require cell–cell interactions. Molecular interactions at the contact interface or initiated by paracrine signaling mediate cellular cross-talk and trigger a series of well-orchestrated downstream signaling events. The magnitude and dynamics of these signals promote and coordinate immune cell activation, and underlie a broad array of functional outcomes, such as target cell elimination, secretory activity, and proliferation. Understanding how these interaction events are transduced into functional responses demands correlated measurements at different stages as these responses unfold. In this talk, I will describe a set of micro-technologies we have developed to study immune cell communication and ensuing effector functions at the single-cell level, and will highlight example applications of these technologies particularly on immune cell activation dynamics and multiplexed proteomic profiling.