HIV/AIDS has become firmly established in both urban and rural areas in Tanzania. The alarming spread of the virus in trading centers and border towns and along transportation routes is fueling the epidemic. Recent data from Mbeya Region, which is now benefiting from large-scale effective intervention, indicate an HIV prevalence of 68 percent among commercial sex workers. Although HIV prevalence in Zanzibar is considerably lower than it is on the mainland, numerous risk factors there point to a significant increase of HIV infections if the quality and scope of interventions are not upgraded. While Tanzanians have lived with a serious generalized HIV/AIDS epidemic for the past twenty years, there has been little perceptible sense of national urgency to address this critical problem. Recently, however, the Government of Tanzania has improved its commitment to fighting HIV/AIDS. The president of Tanzania in 2003 declared HIV/AIDS a national disaster and both the National AIDS Control Program and the Tanzania Commission for AIDS (TACAIDS) are intensifying the national response. The traditional reliance on central and hierarchical leadership to drive the national agenda has minimized the development of shared leadership and the empowerment of civil society, communities, and decentralized structures to address the HIV/AIDS epidemic. The recent creation of TACAIDS, the Zanzibar AIDS Commission (ZAC), and recent global initiatives--including the President’s Emergency Plan for AIDS Relief--may provide renewed hope for strengthening multisector and multilevel responses to the HIV/AIDS challenge. As importantly, Tanzania can build on several successful demonstration projects and large-scale interventions and related lessons to guide the scaling up of effective interventions.