Tom Dishion, a pioneer in prevention science, was one of the first to recognize the importance of adapting interventions to the needs of individual families. Building towards this goal, we suggest that prevention trials be used to assess baseline target moderated mediation (BTMM), where preventive intervention effects are mediated through change in specific targets, and the resulting effect varies across baseline levels of the target. Four forms of BTMM found in recent trials are discussed including compensatory, rich-get-richer, crossover, and differential iatrogenic effects. A strategy for evaluating meaningful preventive effects is presented based on preventive thresholds for diagnostic conditions, midpoint targets and proximal risk or protective mechanisms. Methods are described for using the results from BTMM analyses of these thresholds to estimate indices of intervention risk reduction or increase as they vary over baseline target levels, and potential cut points are presented for identifying subgroups that would benefit from program adaptation because of weak or potentially iatrogenic program effects. Simulated data are used to illustrate curves for the four forms of BTMM effects and how implications for adaptation change when untreated control group outcomes also vary over baseline target levels.