The United Nations Millennium Development Goals (MDGs) are a series of 8 goals and 18 targets aimed at ending extreme poverty by 2015, and there are 48 quantifiable indicators for monitoring the process. Most of the MDGs are health or health-related goals. Though the MDGs might sound ambitious, it is imperative that the world, and sub-Saharan Africa in particular, wake up to the persistent and unacceptably high rates of extreme poverty that populations live in, and find lasting solutions to age-old problems. Extreme poverty is a cause and consequence of low income, food insecurity and hunger, education and gender inequities, high disease burden, environmental degradation, insecure shelter, and lack of access to safe drinking water and basic sanitation. It is also directly linked to unsound governance and inequitable distribution of public wealth. While many regions in the world will strive to attain the MDGs by 2015, most of the countries in sub-Saharan Africa, with major human development challenges associated with socio-economic disparities, will not. Zambia’s MDG progress reports of 2003 and 2005 show that despite laudable political commitment and some advances made towards achieving universal primary education, gender equality, improvement of child health and management of the HIV/AIDS epidemic, it is not likely that Zambia will achieve even half of the goals. Zambia’s systems have been weakened by high disease burden and excess mortality, natural and man-made environmental threats and some negative effects of globalization such as huge external debt, low world prices for commodities and the human resource “brain drain”, among others. Urgent action must follow political will, and some tried and tested strategies or “quick wins” that have been proven to produce high positive impact in the short term, need to be rapidly embarked upon by Zambia and other countries in sub-Saharan Africa if they are to achieve the Millennium Development Goals.