BackgroundDespite being entirely preventable, canine rabies still kills 55,000 people/year in developing countries. Information about local beliefs and practices can identify knowledge gaps that may affect prevention practices and lead to unnecessary deaths.Methodology/Principal FindingsWe investigated knowledge, attitudes and practices related to rabies and its prevention and control amongst a cross-section of households (n = 5,141) in urban and rural areas of central, southern and northern Tanzania. Over 17% of respondents owned domestic dogs (average of 2.3 dogs/household),>95% had heard about rabies, and>80% knew that rabies is transmitted through dog bites. People who (1) had greater education, (2) originated from areas with a history of rabies interventions, (3) had experienced exposure by a suspect rabid animal, (4) were male and (5) owned dogs were more likely to have greater knowledge about the disease. Around 80% of respondents would seek hospital treatment after a suspect bite, but only 5% were aware of the need for prompt wound cleansing after a bite. Although>65% of respondents knew of dog vaccination as a means to control rabies, only 51% vaccinated their dogs. Determinants of dog vaccination included (1) being a male-headed household, (2) presence of children, (3) low economic status, (4) residing in urban areas, (5) owning livestock, (6) originating from areas with rabies interventions and (7) having purchased a dog. The majority of dog-owning respondents were willing to contribute no more than US$0.31 towards veterinary services.Conclusions/SignificanceWe identified important knowledge gaps related to, and factors influencing the prevention and control of rabies in Tanzania. Increasing knowledge regarding wound washing, seeking post-exposure prophylaxis and the need to vaccinate dogs are likely to result in more effective prevention of rabies; however, greater engagement of the veterinary and medical sectors is also needed to ensure the availability of preventative services.