We report the first two indigenously acquired cases of melioidosis in Taiwan, diagnosed by positive culture and biochemically identified using the ID 32 GN system (BioMerieux Vitek Inc, Hazelwood, MO, USA). The first patient was a 75-year-old Chinese woman who had not travelled abroad since her arrival from mainland China (San-Tung province) 47 years ago. She presented with spontaneous bacterial peritonitis and hepatitis C-related liver cirrhosis with septic shock. Burkholderia pseudomallei (formerly Pseudomonas pseudomallei) was isolated from cultures of both blood and ascites fluid. The second patient, a 70-year-old Chinese man, presented with right lower lobar pneumonia complicated with empyema and septic shock. Blood cultures grew B. pseudomallei. Both patients had underlying diabetes mellitus; one also had liver cirrhosis and chronic renal failure, while the other had a renal stone. The first patient died of refractory septic shock prior to diagnosis. The second patient survived with the use of intravenous ceftazidime for 30 days, followed by oral amoxicillin-clavulanic acid for a further 3 months. These cases serve as a reminder to clinical physicians that melioidosis is now no longer exclusive to patients with a history of travel to endemic areas. A high index of clinical suspicion is required for early diagnosis and treatment in order to reduce the mortality and improve clinical outcome.