To better define infectious diseases of concern in Thailand, trends in the mortality rate during 1958-2009 were analyzed by using data from public health statistics reports. From 1958 to the mid-1990s, the rate of infectious disease-associated deaths declined 5-fold (from 163.4 deaths/100,000 population in 1958 to 29.5/100,000 in 1997). This average annual reduction of 3.2 deaths/100,000 population was largely attributed to declines in deaths related to malaria, tuberculosis, pneumonia, and gastrointestinal infections. However, during 1998-2003, the mortality rate increased (peak of 70.0 deaths/100,000 population in 2003), coinciding with increases in mortality rate from AIDS, tuberculosis, and pneumonia. During 2004-2009, the rate declined to 41.0 deaths/100,000 population, coinciding with a decrease in AIDS-related deaths. The emergence of AIDS and the increase in tuberculosis- and pneumonia-related deaths in the late twentieth century emphasize the need to direct resources and efforts to the control of emerging and re-emerging infectious diseases.