We study the method of layer potentials for manifolds with boundary and cylindrical ends. The fact that the boundary is non-compact prevents us from using the standard characterization of Fredholm or compact pseudo-differential operators between Sobolev spaces, as, for example, in the works of Fabes-Jodeit-Lewis and Kral-Wedland . We first study the layer potentials depending on a parameter on compact manifolds. This then yields the invertibility of the relevant boundary integral operators in the global, non-compact setting. As an application, we prove a well-posedness result for the non-homogeneous Dirichlet problem on manifolds with boundary and cylindrical ends. We also prove the existence of the Dirichlet-to-Neumann map, which we show to be a pseudodifferential operator in the calculus of pseudodifferential operators that are “almost translation invariant at infinity”.