The year 1898 was one of the most significant years in the history of malariology. One hundred years later scientists gathered at the Accademia Nazionale dei Lincei, Rome, to commemorate the Malariology Centenary. This paper provides a short overview of some of the key developments and discoveries in malaria research which took place at the end of the 19th century. The major contributions of Alphonse Laveran, Patrick Manson, Ronald Ross, Battista Grassi and a number of scientists of the Italian School of Malariology to the understanding of the transmission of malaria by Anopheles mosquitoes are described. This paper also highlights the importance of an historical perspective in furthering our understanding of the 'Malaria Challenge after One Hundred Years of Malariology'.