“Preventing and Treating Women’s Drug and Substance Abuse,” presents strategies and programs aimed at the primary, secondary, and tertiary prevention of drug and substance abuse among women. Specific strategies for women are identified and discussed, with attention to women’s different reasons for initiating drug and substance use; continuing use as it becomes increasingly harmful to themselves, their families, and communities; and discontinuing use. A variety of: (1) recently developed pharmacotherapeutic approaches; and (2) traditional and new forms of psychotherapy and counseling for women are described and discussed. The goal of meeting the unique needs of women, who may have greater success associated with certain types of intervention—and, by corollary, less success with others—is a major focus. Thus, specific prevention and treatment approaches developed for sub-groups of women (e.g. Hispanic women; lesbian women; older women; trans women; women of African continental descent) are presented and discussed. To actively address many of these related issues, we developed and present the New Millennial Interactive Model of Women’s Drug and Substance Abuse. We specifically developed the interactive model to facilitate a better understanding among readers of the many interacting variables that influence a woman’s use of the drugs and substances of abuse. Based on our comprehensive analysis and reflective synthesis of the data presented in this text, the model is comprised of four major variable dimensions. Specifically, attention is given to the Woman Dimension and its interaction with the other three dimensions—the Drug or Substance of Abuse Dimension, the Societal Dimension, and the Time Dimension—in order that associated, clinically significant interactions and relationships can be more fully and properly identified and understood in an actual clinical context. This approach allows for the optimal analysis of contributory factors related to the various patterns of drug and substance abuse noted among women in the U.S.— both individually (e.g., a college/university student) and in groups (e.g., homeless women; incarcerated women; older women).