In 2003 the Centers for Disease Control and Prevention (CDC) launched a new HIV prevention strategy that focused prevention efforts on people living with HIV. In response to a Health Resources and Services Administration (HRSA)/Special Projects of National Significance (SPNS) initiative, a program development team in Philadelphia created the Protect and Respect program. The program integrates multiple-level prevention strategies and is tailored to address the strengths of HIV-positive women and the challenges they face to implementing behavior changes. The goal of Protect and Respect is to decrease sexual behavior that puts HIV-positive women at risk for sexually transmitted infections (STIs) and puts others at risk for HIV transmission. The three components of the program are: brief HIV prevention messages delivered by clinicians in the context of routine medical visits; a group-level intervention (GLI) delivered by a Health Educator; and a Peer-led support group. This paper details the process of developing the three program components and describes the valuable lessons learned through the development and implementation process.