Experience with delivery of renal replacement therapy (RRT) in support of combat operations by the U.S. military has not been reported since the 1970s. We describe the tri-service military medical experience with RRT in support of Operation Iraqi Freedom. Through December 31, 2006, RRT was provided to 12 individuals inside the theater of operations. Navy medical personnel provided RRT to three patients (two U.S. active duty service members and one host nation individual) aboard the USNS Comfort, a mobile level 4 hospital. Dialysis was performed using conventional single-pass hemodialysis machines equipped with portable reverse osmosis systems. Army and Air Force medical personnel provided RRT to nine patients in theater (eight host nation patients and one U.S. active duty service member), using peritoneal dialysis and continuous renal replacement therapy (CRRT), not requiring trained renal nurses or technicians. Originally, U.S. military personnel with acute kidney injury (AKI) who were evacuated from theater to Landstuhl Regional Medical Center (LRMC), or those who developed AKI at LRMC were transferred to the German civilian medical system, if RRT was required. After creation of a rapid-response dialysis team and, later, positioning of a full-time active duty reserve nephrologist at LRMC, 16 patients received RRT at LRMC. None had required RRT in theater. Renal failure requiring RRT during combat operations remains an unusual but serious event, calling for flexibility in the provision of care. Notably, the Operation Iraqi Freedom experience has highlighted the needs of injured host nation patients with AKI and future military medical planning will need to account for their intratheater renal care.