Instructions are known to have a profound impact on human behavior. Nevertheless, research on the effects of instructions is relatively scarce and scattered across different areas of research in psychology and neuroscience. The current issue of this journal contains six papers that review research on instructions in different research areas. In this introduction to the special issue, we provide the outline of a framework that focuses on five components that can be varied in research on this topic (sender, message, receiver, context, and outcome). The framework brings order to the boundless potential variability in research on the effects of messages (i.e., it has heuristic value) and highlights that past research explored only a tiny fraction of what is possible (i.e., it has predictive value). Moreover, it reveals that research in different areas tends to examine different instantiations of the five components. The latter observation implies that much can be gained from closer interactions between researchers from different areas.