We present a novel ecosystem-specific framework for developing nutrient criteria from biological thresholds and predictive modeling (BTPM) and an application of this framework to lakes in Michigan, U.S. The four main components for the BTPM framework are: (1) to predict each ecosystem s expected nutrient concentration in the absence of human effects using a predictive model, (2) to identify important biological thresholds along a nutrient gradient (i.e., biological [BIO] benchmarks), (3) to determine each ecosystem s current nutrient concentration, and (4) to use the above information to derive a nutrient criterion for each ecosystem using the BTPM algorithm. The BTPM framework is extremely flexible in that it can be applied to any aquatic ecosystem type or nutrient and the four components can be implemented in a variety of ways. Our BTPM framework has two additional features: it recognizes that prior to human disturbance, ecosystems varied in their natural nutrient concentrations, and it incorporates risk into the decision-making process. In the simplest scheme, a nutrient criterion is set at a BIO benchmark greater than the expected nutrient concentration. However, to protect ecosystems more conservatively, a criterion is set at current lake nutrient concentrations if current is less than the BIO benchmark. In our application of the BTPM framework, we developed total phosphorus (TP) criteria for a diverse set of 374 lakes in MI. The expected lake TP concentrations in the absence of human effects ranged from 3 µg L-1 to 24 µg L-1, suggesting that a single criterion approach would not be appropriate.We found two predominant benchmarks in the biological data along the TP gradient, one for zooplankton metrics at 8 µg L-1, and one for phytoplankton metrics at 18 µg L-1. We present the sequence of analyses and decisions that could be used to apply this approach in a management context using Michigan lakes as an example.