We construct a class of Hamiltonians that describe the photodetection process from beginning to end. Our Hamiltonians describe the creation of a photon, how the photon travels to an absorber (such as a molecule), how the molecule absorbs the photon, and how the molecule after irreversibly changing its configuration triggers an amplification process-at a wavelength that may be very different from the photon's wavelength-thus producing a macroscopic signal. We use a simple prototype Hamiltonian to describe the single-photon detection process analytically in the Heisenberg picture, which neatly separates desirable from undesirable effects. Extensions to more complicated Hamiltonians are pointed out.