Urosepsis in adults comprises approximately 25% of all sepsis cases and in most cases is due to complicated urinary tract infections (UTIs). In this paper we review the optimal management of urosepsis from the urological point of view. Urosepsis is often due to obstructed uropathy of the upper or lower urinary tract. The treatment of urosepsis comprises four major aspects: 1. Early goal-directed therapy; 2. Optimal pharmacodynamic exposure to antimicrobials both in blood and in the urinary tract; 3. Control of complicating factors in the urinary tract; 4. Specific sepsis therapy. Early tissue oxygenation, appropriate initial antibiotic therapy and rapid identification and control of the septic focus in the urinary tract are critical steps in the successful management of a patient with severe urosepsis. To achieve this goal an optimal interdisciplinary approach encompassing the emergency unit, urological specialties and intensive-care medicine is necessary.