Problems implementing DNA computers stem from the physical nature of molecules and their reactions. The present theory of computation requires assumptions that, at best, are extremely crude approximations of the physical chemistry. Here, I consider the hypothesis that discarding those assumptions in favor of more physically realistic descriptions would produce a more comprehensive theory of computing, yielding both theoretical insights and help in designing better molecular computers. I describe the discordances between the theories of physical biochemistry and computation, indicate some elements of a more comprehensive theory, and discuss some of the challenges the construction of a unified theory faces.