Uganda has some of the highest reported malaria transmission rates in the world. Methods: We reviewed published and un-published reports to provide a historical perspective and evolution of malaria case management strategies/policies in Uganda. Review findings: In the 1990s, uncomplicated malaria treatment was hampered by widespread parasite resistance to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP). Paradoxically, faced with this challenge, the country changed the first-line regimen, in 2000, to CQ+SP and adopted home based management of fever (HBMF) for children < 5 years old. HBMF increased the proportion accessing CQ+SP within 24 hours from 7% in 2001 to 39% in 2003. However, after another policy shift, in 2004, to Artemether-Lumefantrine (AL), HBMF is to date implemented in only 34 of 112 districts. The private sector supports first treatment contact for 40-50% of fevers. However, engaging private sector providers remains challenging. Consequently, by 2011, only 30% of febrile children took AL on the same/next day after symptom onset. In 2011 there was a policy shift from presumptive treatment to parasite-based diagnosis. Following the policy change, the proportion of tests by rapid diagnostic tests (RDTs) increased to about 55% compared to 30% by microscopy. However a major challenge remains clinician’s adherence to test results. Reassuringly, AL remains efficacious. In 13 studies conducted between 2002 and 2010, the median PCR corrected day 28 efficacy was 98% (range: 71.9%–100%).