Crop yield losses (YL) result from the dynamic interactions between agrophysiological processes and damage mechanisms. The former translate into levels of attainable yield (Ya), which are reflections of shifting production situations (PS). The latter depend on the biological diversity of harmful organisms leading to injury profiles (IP), which also depend on PS. Complex interactions are therefore at play in many cases. PS components include technology shifts (T), labor availability (L), water supply (W), mineral fertilizers (F), pesticides (P), and varietal improvement (V). Agricultural adaptation to increasing food, feed, fiber, and energy demand is making use of various combinations of these components, some of them being directly dependent on climate change (C). For wheat in France, shifts in PS (F, P, V) lead to small Ya variation, and to less diverse, weaker PSs, translating in reduced YL. For lowland rice in Asia, highly variable PSs (C, T, L, W, F, P, V) correspond to large differences in Ya (increases or decreases), and very different IPs however translating into similar YL. Groundnut in West Africa, by contrast, may experience strong increase in Ya from improved PS (T, L, F), at the cost of intensified IP and higher YL. A broad framework for YL analysis is presented, showing the need and the value of a systems-based crop health assessment, as novel production systems are being designed for a growing world population under global change.