Introduction Intermittent presumptive treatment (IPT) for malaria during pregnancy (IPTp) is advocated against malaria. Yet, concerns prevail regarding safety, efficacy, and costs of the recommended anti-malarial interventions in economic, social and multi-faceted health contexts. Objective This chapter elucidates the views of frontline healthcare workers (HWs) and antenatal care (ANC) clients regarding feasibility of implementing anti-malarial drugs in formal healthcare settings of Tanzania, including the scaling-up IPTp delivery in attempt to attain higher population coverage. Emphasis is on efficacy, safety and cost issues related to SP for IPTp. Methods Semi-structured interviews with HWs and pregnant women at ANC clinics and investigators' observations in the fields were conducted. Content analysis was done on qualitative information whereas quantitative data were analyzed using computer software programs. Results The respondents expressed positive and negative attitudes towards IPTp currently in practice. The reported positives of IPTp were related to: sulfadoxine-pyrimethamine (SP) - a drug of choice being more efficacious than other anti-malarial drugs; easy deliverability in terms of users taking a full dose once; saving lives of women, fetuses and newborn babies; and un-bitter taste. The negatives include the: (i) perception about SP causing adverse treatment outcomes, this lowering users' adherence to treatment schedules, including directly observed treatment; (ii) perceived possible adverse reactions if SP is used by the users who take alcoholic drinks; (iii) increasing- parasites resistance to SP and HIV infections lowering public trust in SP; (iii) health facilities (HFs), especially the private ones facing SP shortages for free delivery, adding costs mainly to the service users and partly HWs who are forced to pay out of their pockets; (iv) HFbased IPTp services forcing pregnant women who reside far away to incur additional costs on re-visiting HFs, including the costs on transport, foods and/or drinks, besides purchasing SP elsewhere when the HFs concerned are out of stock of SP, and time lost for waiting for services. Moreover, user-fees for ANC services other than IPTp seemed to dissuade some potential clients to attend clinic. Additional findings and discussions are presented. Conclusion When institutionalizing policies, national and international authorities sometimes under-rate the operational barriers to the recommended interventions in local settings. This study reveals that the social perceptions on- and the real deficiencies of anti-malarial drug efficacy, safety and costs are a challenge for rolling back malaria in Tanzania, as elsewhere in Africa.