Wireless connectivity has traditionally been regarded as an opaque data pipe carrying messages, whose context-dependent meaning and effectiveness have been ignored. Nevertheless, in emerging cyber-physical and autonomous networked systems, acquiring, processing, and sending excessive amounts of distributed real-time data, which ends up being stale or useless to the end user, will cause communication bottlenecks, increased latency, and safety issues. We envision a communication paradigm shift, which makes the semantics of information (i.e., the significance and usefulness of messages) the foundation of the communication process. This entails a goal-orient-ed unification of information generation, transmission, and reconstruction, by taking into account process dynamics, signal sparsity, data correlation, and semantic information attributes. We apply this structurally new, synergetic approach to a communication scenario where the destination is tasked with real-time source reconstruction for the purpose of remote actuation. Capitalizing on semantics-empowered sampling and communication policies, we show significant reduction in both reconstruction error and cost of actuation error, as well as in the number of uninformative samples generated.