Despite the increased number of International Environmental Regimes (IERs), gradually worsening environmental indicators have made the effectiveness of regimes a current and controversial issue. Doubtlessly, regimes are one of the most significant tools of global environmental governance. Enabling interstate cooperation, increasing knowledge about ecological problems, keeping these problems on the agenda, and providing relative improvement in some issue areas are the positive outcomes of regimes. However, IERs are institutions that are currently based on the stable and predictable earth system conditions of the Holocene Epoch. Therefore, IERs are unlikely to operate effectively under the unpredictable and unstable conditions of the new, Anthropocene era. Based on this argument, this article attempts to reveal that the effectiveness of regimes depends on their capacity to cope with the challenges of the Anthropocene. Regimes can confront these challenges by adopting a holistic earth system perspective based on the integrity of socio-ecological systems and planetary boundaries.