During the centenary year of the University of Pretoria (2008), the Department of Science of Religion and Missiology took stock of its activities during the past 55 years, since the first professor in Missiology, H.D.A. du Toit, was appointed. In his wake a number of missiologists followed – C.W.H. Boshoff, D. Crafford, P.G.J. Meiring, J.J. Kritzinger, P.J. van der Merwe, A.S. van Niekerk and C.J.P. Niemandt – each of whom has contributed to the formation of hundreds of ministers and missionaries, as well as to the development of missiology and science of religion in South Africa through their research and writings. In this article, the place of missiology among the other theological disciplines at the University of Pretoria is discussed, together with an analysis of the nature and the mandate of missiology and science of religion in South Africa in our day. This article discusses five specific challenges to missiology at the beginning of the third millennium, namely to maintain its theological ‘roots’; to operate in close relationship with the church; to focus on our African context; to concentrate on a relevant agenda; and to develop a responsible methodology. Attention is given to some of the more important publications by members of the Department.