How robust is our assessment of impacts to ecosystems and species from a rapidly changing climate during the 21st century? We examine the challenges of uncertainty, complexity and constraints associated with applying climate projections to understanding future biological responses. This includes an evaluation of how to incorporate the uncertainty associated with different greenhouse gas emissions scenarios and climate models, and constraints of spatiotemporal scales and resolution of climate data into impact assessments. We describe the challenges of identifying relevant climate metrics for biological impact assessments and evaluate the usefulness and limitations of different methodologies of applying climate change to both quantitative and qualitative assessments. We discuss the importance of incorporating extreme climate events and their stochastic tendencies in assessing ecological impacts and transformation, and provide recommendations for better integration of complex climate–ecological interactions at relevant spatiotemporal scales. We further recognize the compounding nature of uncertainty when accounting for our limited understanding of the interactions between climate and biological processes. Given the inherent complexity in ecological processes and their interactions with climate, we recommend integrating quantitative modeling with expert elicitation from diverse disciplines and experiential understanding of recent climate-driven ecological processes to develop a more robust understanding of ecological responses under different scenarios of future climate change. Inherently complex interactions between climate and biological systems also provide an opportunity to develop wide-ranging strategies that resource managers can employ to prepare for the future.