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Climate change is one of the biggest challenges of our times. Its impact on human populations is not yet completely understood. Many studies have focused on single aspects with contradictory observations. However, climate change is a complex phenomenon that cannot be adequately addressed from a single discipline’s perspective. Hence, we propose a comprehensive conceptual framework on the relationships between climate change and human responses. This framework includes biological, psychological, and behavioural aspects and provides a multidisciplinary overview and critical information for focused interventions. The role of tipping points and regime shifts is explored, and a historical perspective is presented to describe the relationship between climate evolution and socio-cultural crisis. Vulnerability, resilience, and adaptation are analysed from an individual and a community point of view. Finally, emergent behaviours and mass effect phenomena are examined that account for mental maladjustment and conflicts.