The evaluation, which has been designed and funded by the Center for Substance Abuse Prevention, involves seven sites that will implement mentoring programs which meet broad criteria intended to provide information on the effectiveness of alternative ways of delivering mentoring services. The major objectives of the MSE are to describe the similarities and differences in the seven mentoring programs and the rationale for local variations; to document the implementation of the programs and generate lessons on effective implementation procedures; to document the degree to which participating youth reported lower substance-use rates and strengthened protective factors compared with control groups; and to identify effective mentoring intervention principles and practices. In describing how these proposed MSE objectives will be met, this article first reviews the background for the evaluation, and it then presents an overview of the conceptual framework and MSE quasi-experimental design. This is followed by an outline of the evaluation measures in the context of the mentoring intervention framework. The article next describes the analyses that will be used to test program outcomes, identify variations in outcome, and draw lessons on differing degrees of effectiveness related to mentoring design and implementation characteristics. 1 table, 1 figure, and 33 references