Determining dynamic structural changes along with the functional movements in biological systems has been a significant challenge for scientists for several decades. Utilizing vibrational coupling with the aid of 2D IR probe pairs has aided in uncovering structural dynamics and functional roles of chemical moieties involved in actions such as membrane peptide folding and transport, ion and water transport, and drug-protein interactions. Both native and non-native vibrational probe pairs have been developed for infrared studies, and their efficacy has been tested in various systems. With these probe pairs, 2D IR spectroscopy captures frozen snapshots of the structural events involved in biological function through vibrational coupling and correlated spectral diffusion. In this Perspective, different treatments of vibrational coupling and coupling models will be addressed, and a review of some of the specific vibrational probe pairs used to study these coupling mechanisms is presented. Overall, the intrinsic molecular dynamics detected on these ultrafast time scales will provide an atomic level view of how chosen structures traverse reaction paths. Thus, it is important to evaluate and assess the accuracy of the different vibrational coupling models and their consistency with the prediction of different molecular structures.