This chapter complements the detailed behavioral responses presented in Chap. 10 by identifying their potential cumulative impact and biological significance. While essential for a comprehensive impact assessment and population viability analyses, empirical quantification of cumulative impact is rare, due to a lack of long-term monitoring studies. This chapter presents the latest methodological framework to assess the biological significance of short- and long-term effects of acoustic disturbance at the population level. The chapter provides examples of empirical studies based on a small sample of marine mammal systems (e.g., northern elephant seals and Sarasota dolphins) that have been subjected to robust, longitudinal studies. Attempts to establish links between short-term responses and long-term consequences based on these systems are also presented along with the challenges of their parametrization. The scarcity of data presents a true challenge in environmental management and can stymie the impact assessment of different noise-generating marine activities. However, considering cumulative impact, at least via a modeling approach, may help triage conservation efforts and stressors’ mitigation. Moreover, alternative management scenarios developed through stakeholder participation and coupled with expert-driven consultations can provide empirical support to different management actions.