In April 1953, Watson and Crick largely defined the program of 20th century biology: obtaining the blueprint of life encoded in the DNA. Fifty years later, in 2003, the sequencing of the human genome was completed. Like any major scientific breakthrough, the sequencing of the human genome raised many more questions than it answered. I'll brief you on some of the big open problems in cell and developmental biology, and I'll explain why approaches, tools, and ideas from the physical sciences are currently reshaping biological research. Super-resolution light microscopies are revealing the intricate spatial organization of cells, single-molecule methods show how molecular machines function, and new probes are clarifying the role of mechanical forces in cell and tissue function. At the same time, Physics stands to gain beautiful new problems in soft condensed matter, quantum mechanics, and non-equilibrium thermodynamics.