The very recent development of Cyber-Physical Systems (CPS) provides a smart infrastructure connecting abstract computational artifacts with the physical world. The solution to CPS must transcend the boundary between the cyber world and the physical world by providing integrated models addressing issues from both worlds simultaneously. This needs new theories, conceptual frameworks and engineering practice. In this paper, we set out the key requirements that must be met by CPS systems, review and evaluate the progress that has been made in the development of theory, conceptual frameworks and practical applications. We then discuss the need for semantics and a proposed approach for addressing this. Grand challenges to informatics posed by CPS are raised in the paper.