The hydrological cycle within a basin is a complex interaction of climate patterns, basin characteristics, and human activities. Significant impacts on water distribution and yield have been noticed lately due to climate variability leading to global warming and shifting precipitation patterns, coupled with anthropogenic interventions. Changes in the river flow, primarily due to human water use and, in some cases, climate change, have been significant in arid and semi-arid regions. Assessing the impact of climate and land use change on streamflow involves various approaches, such as trend analysis, hydrological indicator-based analysis, and hydrological modeling. However, each approach comes with its strengths and limitations. This book chapter explores the pivotal role of headwater catchments globally, highlighting the impact of climate change, human activities, and land use changes in modifying streamflow regimes in the headwater catchments. Along with the foundational physics of different processes in headwater catchment, a meta-synthesis from diverse case studies and scientific research, the chapter also explores strategies for adaptation and mitigation, emphasizing the need for interdisciplinary collaboration and effective policy measures. By providing a comprehensive overview of the causes and impacts of streamflow regime shifts in headwater catchments, this chapter is an essential resource for researchers, practitioners, and policymakers seeking to better understand and address this critical issue in a changing environment.