Natural photochemical processes often require special instrumentation to monitor them at a Suitable time scale. Rapid-scan FTIR difference spectroscopy is one of the preferred techniques to obtain rich Structural information in the scale of milliseconds about photochemical processes of complex natural systems. The difference spectra obtained by this technique enhance the fine spectroscopic changes undergone during the process but require powerful data analysis methodologies to take full advantage of the information provided. Hybrid hard- and soft-modeling methodologies allow for coping with difficulties linked to the nature of the time-resolved measurement and to the complexity of the kinetic model describing the natural photochemical process. Thus, this methodoloy presents the following advantages: (a) handles difference spectra, taking into account the consequences of the lack of measurement about the initial stage of the process, (b) models events of the process that may be defined by a kinetic model (by hard modeling) and events that do not obey a mechanistic behavior (by soft modeling), (c) adapts to the photoaccumulation/relaxation stages of reversible photochemical processes, and (d) works simultaneously with series of experiments performed in different conditions and showing different kinetic behavior. The results of this data treatment provide complete kinetic information oil the photochemical processes, e.g.. rate constants, and a global Picture of the difference spectra and the concentration profiles linked to each of the events (hard or soft modeled) contributing to the measured signal. The performance of the combination of time-resolved differential FTIR and hybrid hard and soft modeling is shown in a complex case Study related to the photosynthetic activity of the reaction center of the purple bacteria Rhodobacter sphaeroides.