We propose orbital fluctuations in a multiband ground state as the superconducting pairing mechanism in the new iron-based materials. We develop a general SU(4) theoretical framework for studying a two-orbital model and discuss a number of scenarios that may be operational within this orbital fluctuation paradigm. The orbital and spin symmetry of the superconducting order parameter is argued to be highly nonuniversal and dependent on the details of the underlying band structure. We introduce a minimal two-orbital model for the Fe-pnictides characterized by nondegenerate orbitals that strongly mix with each other. They correspond to the iron "d(xy)" orbital and to an effective combination of "d(zx)" and "d(zy)," respectively. Using this effective model we perform random-phase-approximation calculations of susceptibilities and effective pairing interactions. We find that spin and orbital fluctuations are, generally, strongly coupled and identify the parameters that control this coupling as well as the relative strength of various channels.