Melioidosis, caused by the bacterium Burkholderia pseudomallei, is a disease of the tropics that rarely occurs in the United States. Disease may occur years or decades after exposure and can appear in acute, chronic, relapsing or reactivated forms, which makes diagnosis more problematic. We report on the clinical aspects of a case of reactivated melioidosis, diagnosed approximately 36 years after initial exposure and after a recently published case with a purported latency of 62 years. Our case patient highlights the clinically complex picture often presented by melioidosis patients, the difficulties in laboratory identification of the causative pathogen, and challenges in provision of appropriate antibiotic therapy for a prolonged period. We survey the current literature with regard to melioidosis epidemiology, diagnosis, and treatment, and report on several cases of reactivation melioidosis not included in previous reviews. We also discuss the clinical and public health aspects of Burkholderia pseudomallei as a Category B agent with potential for use as biological weapon and the importance of physicians immediately reporting any suspect cases to public health officials to facilitate more rapid assessment and response.