Burkholderiaspecies, notablyBurkholderia cepaciaandBurkholderia gladioli,are important pathogens in patients with chronic granulomatous disease (CGD).Burkholderia pseudomallei,the causative agent of melioidosis, is endemic in Southeast Asia and northern Australia but is a rare pathogen in other parts of the world. We describe the occurrence ofB. pseudomalleiinfection in a Puerto Rican patient with CGD. This is one of only a small number of documented cases of melioidosis autochthonous to the Americas and is the first reported case ofB. pseudomalleiinfection in a CGD patient from the Americas. We conclude thatB. pseudomallei,likeB. cepaciaandB. gladioli,should be considered a potential pathogen in patients with CGD and that melioidosis should be considered in the differential diagnosis for ill residents of or travelers to Puerto Rico.