Although sporadic human infection due to Burkholderia cepacia has been reported for many years, it has been only during the past few decades that species within the B. cepacia complex have emerged as significant opportunistic human pathogens. Individuals with cystic fibrosis, the most common inherited genetic disease in Caucasian populations, or chronic granulomatous disease, a primary immunodeficiency, are particularly at risk of life-threatening infection. Despite advances in our understanding of the taxonomy, microbiology, and epidemiology of B. cepacia complex, much remains unknown regarding specific human virulence factors. The broad-spectrum antimicrobial resistance demonstrated by most strains limits current therapy of infection. Recent research efforts are aimed at a better appreciation of the pathogenesis of human infection and the development of novel therapeutic and prophylactic strategies.