This paper develops a unified framework for studying robustness of the input-to-state stability (ISS) property and presents new results on robustness of ISS to slowly varying parameters, to rapidly varying signals, and to generalized singular perturbations. The common feature in these problems is a time-scale separation between slow and fast variables which permits the definition of a boundary layer system like in classical singular perturbation theory. To address various robustness problems simultaneously, the asymptotic behavior of the boundary layer is allowed to be complex and it generates an average for the derivative of the slow state variables. The main results establish that if the boundary layer and averaged systems are ISS then the ISS bounds also hold for the actual system with an offset that converges to zero with the parameter that characterizes the separation of time-scales. The generality of the framework is illustrated by making connection to various classical two time-scale problems and suggesting extensions.