Multi-dimensional infrared spectra are often modeled in terms of optical response functions. These optical response functions consist of contributions from Liouville pathways that correspond to sequences of impulsive field-matter interactions separated by periods of field-free evolution. These pathways differ with respect to the chromophore’s quantum state during the time intervals between light-matter interactions. However this formulation relies on two key implicit assumptions, namely: (1) that the field-matter interaction is the only way to change the state of the chromophore; (2) that the bath degrees of freedom undergo equilibrium dynamics on the potential surface that corresponds to the chromophore’s ground state. However, in practice irradiative relaxation processes may change the state of the chromophore during the periods of field-free evolution and the dynamics of the bath degrees of freedom during those time field-free periods would be dictated by the adiabatic potential energy surfaces that correspond to the instantaneous quantum state of the chromophore. One therefore expects the system to hop between potential surfaces during the periods of field-free dynamics and the spectra to reflect the dynamics during the resulting inherently nonequilibrium process. In this talk I will describe several alternative mixed quantum-classical formulations of optical response that are able to account for the effect of the above mentioned nonequilibrium dynamics in a self-consistent manner. I will also demonstrate the utility of these formulations via applications to several systems where such nonequilibrium dynamics has a profound effect on the spectra, including (1) The hydrogen stretch of a hydrogen-bonded complex dissolved in a dipolar liquid; (2) The hydroxyl stretch of methanol in methanol/carbon-tetrachloride liquid mixtures; (3) The carbonyl stretches of metal-carbonyl complexes in liquid solution.