The international community has set ambitious goals (Millennium Development Goals) to improve health in developing countries by 2015. Effective and often cheap interventions exist to achieve these goals. In the mainland of Tanzania, one of the poorest countries of the world, we explored the human resources challenges of expanding the coverage of such priority interventions. We projected human resources for health (HRH) availability using a standard approach and estimated human resource requirements using a novel method (QTP) that produces estimates by task-specific skill categories and explicitly considers productivity. In this paper, we present the findings of the case study in Tanzania and discuss the strengths and weaknesses of the QTP model. On the whole, the HRH challenge of expanding priority interventions in mainland Tanzania is daunting. HRH requirements exceed by far the estimates of HRH availability for 2015. The scaling up of the HIV/AIDS related intervention cluster, in particular the treatment and care of people living with HIV/AIDS, was the primary driver of increases in HRH requirements between the study's base year, 2002, and 2015, and thus of the overall imbalance. Scenario analysis points to three key areas for change in HRH policy and practice to reduce future imbalances: the increment-attrition balance, staff and service productivity, and the match between task-specific skill and occupational categories. However, even in an optimistic scenario, human resource availability will limit the extent to which priority interventions can be expanded in the mainland of Tanzania, and the government will not be able to avoid adjusting the globally set targets for service coverage and health outcomes to local realities and priorities.