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Co-limitation is defined as the coincident limitation of biological activity by multiple resources. According to theories of resource optimization, co-limitation should be common as organisms adjust to changes in the availability of resources in the environment. We review the multi-faceted nature of the co-limitation concept and provide a synthesis of recent experimental studies of co-limitation in northern hardwood forests to illustrate the complexities of nitrogen (N) and phosphorus (P) co-limitation and possible responses to environmental stressors such as acid rain, N deposition, elevated CO2, land-use, and climate change. In a factorial nutrient addition experiment, cycling of one nutrient changed in response to addition of the other through synergistic interactions and feedbacks between N and P, including microbial recycling, soil enzyme activity, and foliar nutrient resorption; these responses were suggestive of some degree of N–P co-limitation in these forests. After 8 years of treatment, aboveground growth increased in response to either N or P added individually and even more in response to N + P addition, indicating N–P co-limitation. Surprisingly, fine root growth increased in response to nutrient addition, with significantly greater root growth in N + P plots in five successional stands and in N plots in three mature stands. In contrast, fine litterfall did not respond significantly to nutrient addition. Collectively, these results demonstrate the complexity of the interactions between macronutrients in regulating production processes in forest ecosystems.