Thermally activated escape over a potential barrier is ubiquitous in physical, biological, chemical, and technical processes and its understanding of paramount importance. For example, single-molecule force spectroscopy experiments, and a number of other physical systems are governed by thermally activated transitions out of a metastable state under the action of a steadily increasing external force. This allows to observe the chemical dissociation of two biomolecules at the single-molecule level. In the first part of this work, we address the problem of theoretically modeling and interpreting these experiments. In the second part of this thesis, the technique of path integration is employed to develop an approximation to the instantaneous escape rate that applies to arbitrarily modulated potentials and temperatures. As such systems are far from thermal equilibrium, the physics is not restricted by the second law of thermodynamics and interesting effects can occur. Using our new approximation, several of these effects are discussed and demonstrated.