Renal infection is a common occurrence in autosomal dominant polycystic kidney disease (ADPKD) and often leads to serious complications, including perinephric abscess, septicemia, and death. Important predisposing factors include age, female sex, and recent instrumentation of the urinary tract. Renal infections in ADPKD are most commonly caused by gram-negative enteric organisms. Diagnosis of these infections may be difficult since some patients do not have bacteriuria. Eradication of cyst infections with conventional antibiotic therapy can be difficult despite in vitro sensitivity of responsible organisms to the agents administered. We review recent studies of the anatomic and functional characteristics of renal cysts and discuss their possible relevance to the treatment of renal cyst infections. Finally, we set forth guidelines for the use of diagnostic studies, antimicrobial therapy, and surgical intervention for polycystic kidney infections.