Proteins are nature's workhorses. They enable living systems to use available energy sources and convert energy from one form into another. Understanding the underlying design principles of how proteins have evolved to fulfill the necessary functions of life can provide researchers with new insights into how to enhance the performance of synthetic nanosystems with far greater sophistication. This review summarizes the relationship between various protein functions and the underlying engineering principles of their overall structures. For example, proteins can specifically recognize other biomolecules with a selectivity and affinity several orders of magnitude superior to their synthetic counterparts. Mimicking a protein binding site with a structurally fixed synthetic analogue is insufficient, since structural changes in the active sites enhance molecular recognition and the catalytic activity of proteins. Recent data also show that protein function can be switched by stretching proteins into nonequilibrium states under physiological conditions. Schemes by which the exposure and structure of recognition sites are switched can be implemented in the design of mechanically responsive synthetic and hybrid systems. Motor proteins, finally, are the jewel in nature's crown, as they can convert one free-energy form into another to generate mechanical force. It is thus of considerable interest to integrate the chemically powered engines into synthetic materials and devices. Finally, we have to advance our ability to assemble nanocomponents into functional systems. Again, lessons can be learned from how biology solves the challenge of systems integration.