The presumptive approach was the World Health Organisation (WHO) recommended to the management of malaria for many years and this was incorporated into syndromic guidelines such as the Integrated Management of Childhood Illnesses (IMCI). In early 2010 however, WHO issued revised treatment guidelines that call for a shift from the presumptive to the test-based approach. Practically, this implies that in all suspected cases, the diagnosis of uncomplicated malaria should be confirmed using rapid test before treatment is initiated. This revision effectively brings to an end an era of clinical practice that span several years. Its implementation has important implications for the health systems in malaria-endemic countries. On the basis of research in Ghana and other countries, and evidence from program work, the Ghana National Malaria Control Program has issued revised national treatment guidelines that call for implementation of test-based management of malaria in all cases, and across all age groups. This article reviews the evidence and the technical basis for the shift to test-based management and examines the implications for malaria control in Ghana.