Since determination of the myoglobin structure in 1957, X-ray crystallography, as the anchoring tool of structural biology, has played an instrumental role in deciphering the secrets of life. Knowledge gained through X-ray crystallography has fundamentally advanced our views on cellular processes and greatly facilitated development of modern medicine. In this brief narrative, I describe my personal understanding of the evolution of structural biology through X-ray crystallography—using as examples mechanistic understanding of protein kinases and integral membrane proteins—and comment on the impact of technological development and outlook of X-ray crystallography - dx.doi.org/10.1016/j.cell.2014.10.051 - 2014