Guidelines on prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) are inconsistently implemented in low-income countries. Strategies are needed to improve the uptake of these guidelines to prevent avoidable new HIV infections of infants. In 2010 the World Health Organisation presented its new PMTCT guidelines, offering two options for short courses of antiretroviral prophylaxis: Option A and Option B. Option A consists of antenatal prophylaxis with zidovudine followed by intrapartum and postpartum prophylaxis with single-dose nevirapine and zidovudine plus lamivudine. Option B recommends triple antiretroviral prophylaxis until after finishing breastfeeding. Tanzania has adopted Option A, and it is currently implementing it. A new option termed Option B+ has emerged recently, which recommends providing lifelong antiretroviral treatment to all HIV-positive pregnant women. In this article, we discuss the likely impact of this last PMTCT strategy in rural Africa with an example of an observational cross-sectional analysis in a rural referral hospital in Tanzania aiming to assess the uptake of PMTCT recommendations. Gaps were identified at all steps of the PMTCT pathway. Effective uptake of PMTCT guidelines has been shown to be extremely challenging in this setting. The continuously changing recommendations on PMTCT stress the need for a much simpler and effective approach. We argue in favour of implementing Option B+ in Tanzania. Financial challenges need to be faced, but Option B+ would help to overcome many barriers that prevent guidelines to be implemented in order to increase coverage and ultimately achieve the goal of 'virtual elimination' of mother-to-child transmission in sub-Saharan Africa.