The High Osmolarity Glycerol (HOG) MAP kinase pathway in the budding yeast Saccharomyces cerevisiae is one of the best characterized model signaling pathways. The pathway processes external signals of increased osmolarity into appropriate physiological responses within the yeast cell. Recent advances in microfluidic technology coupled with quantitative modeling, and techniques from reverse systems engineering have allowed yet further insight into this already well-understood pathway. These new techniques are essential for understanding the dynamical processes at play when cells process external stimuli into biological responses. They are widely applicable to other signaling pathways of interest. Here, we review the recent advances brought by these approaches in the context of understanding the dynamics of the HOG pathway signaling.