With respect to meteorological changes and glacier evolution, the southern Pamir Mountains are a transition zone between the Pamirs, Hindu Kush and Karakoram, which are water towers of Central Asia. In this study, we compare runoff and climate trends in multiple time periods with glacial changes reported in the literature. Recent glacier evolution in the Southern Pamirs and its contribution to river runoff are studied in detail. Uncertainties of estimating glacier retreat contribution to runoff are addressed. Runoff trends in the Pamir-Hindu Kush-Karakoram region appear to be a strong proxy for glacier evolution because they exhibit the same spatial pattern as glacial change. There is an anomaly in the North-West Pamirs and Northern Karakoram, showing decreasing runoff trends. In the opposite way, there is a glacier and hydrological change experienced in the Southern Pamirs and Hindu Kush. The prevailing hypothesis for the Karakoram Anomaly, decreasing summer temperatures along with increasing precipitation rates, seems to be valid for the North-Western Pamirs, as well. In the Southern Pamirs, temperature trends have been rising since 1950. Here, the unique water cycle of exclusively winter precipitation does not protect glaciers from accelerated retreat. Snow cover is preset to melt within the seasonal water cycle, due to much lower precipitation amounts falling on glaciers. Therefore, a probable increase in westerly precipitation in both regions causes glacier mass gain in the Northern Pamirs and rising river flows in the Southern Pamirs.