Rift Valley fever (RVF) is a viral notifiable zoonotic disease primarily of domestic ruminants that causes significant socio-economic impacts. Using the 2006-07 outbreak cases, this study aimed to establish the socio-economic impact of RVF and assessing knowledge, attitude and practice of livestock keepers towards controlling RVF in selected areas of Tanzania. Data were collected in Arusha, Manyara and Morogoro regions using questionnaires, focus group discussions and in-depth interviews with key informants. Results indicate that there was little knowledge on disease (all clinical signs scored <50%) and the difference between the three regions was statistically significant (P = 0.00459). Socio-economic impacts of RVF shown by this study included; animal and human deaths, disruption of livestock market chains, inability of pastoralists to achieve their daily demands, inability to obtain protein leading to malnutrition and monetary loss at individual and national level during control of the disease. These findings have demonstrated low knowledge of the community on RVF, thus, more education and engagement is needed in order to develop more effective and efficient control strategies.