Sixty years after the beginning of the molecular biology revolution, physical scientists are becoming attracted to biology again. This time, unlike the situation six decades ago, we know a great deal about the parts and components of the cell. Moreover, the complexity that drove away many physical scientists in the past is now yielding to the reductionist approach, and complexity in itself has become a central research theme in physics. The stage is thus set for the development of renewed efforts at quantification in biological research and at modeling integrated cellular functions. This is the new playground where physical biology and their practitioners will make their impact. Some of the research challenges lying ahead are discussed.