The discovery of the double-helical structure of DNA, the elucidation of the genetic code, and the determination of the three-dimensional structure of several proteins are some of the outstanding achievements of biochemistry and life sciences in the latter half of the last century. Proteins play key roles in almost all the biological processes and the biological function of a protein depends on its conformation which is defined as the three-dimensional arrangement of the atoms of a molecule. The three-dimensional structure, however, is not rigid but fluctuated. Structural fluctuation plays an important role in bio-macromolecules. How about “functional fluctuation” in biological systems? The present review proposes that functional fluctuation is also very important for understanding the mechanism of supramolecules, biological processes in living cells, and the interaction between biological systems. This new theme is pretty well supported by our recent experiments for neuro-immune crosstalk, gene transfection with cationic liposomes, and cell signaling in embryonic stem cells.