Recent years have witnessed a rapidly growing crisis in antimicrobial resistance, especially among microorganisms that cause nosocomial infection. To better understand common risk factors among multiresistant organisms, this review explores risk factors for nosocomial infection with methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococcus, Clostridium difficile, extended-spectrum beta-lactamase-producing gram-negative bacilli, and Candida. This review comprises data from 74 published studies; 53 (71%) were retrospective studies and addressed few risk factors or did not quantify risk. The analysis shows impressive commonality of risk factors across these diverse multiresistant organisms: advanced age; underlying diseases and severity of illness; inter-institutional transfer of the patient, especially from a nursing home; prolonged hospitalization; gastrointestinal surgery or transplantation; exposure to invasive devices of all types, especially central venous catheters; and exposure to antimicrobial drugs, especially cephalosporins. More restricted use of antibiotics, especially cephalosporins, and strategies to prevent medical device-related infection and cross-infection in the hospital would yield benefit with all types of resistant organisms. Preemptive isolation of all patients with risk factors for infection by resistant organisms would very likely reduce secondary spread within the hospital. Conversely, programs that focus on only one organism or one antimicrobial drug are unlikely to succeed. Prospective studies of sufficient size that address all potential risk factors, especially individual anti-infective agents, and that use matched controls who are shown by surveillance cultures to be free of colonization by resistant organisms would enhance understanding of the epidemiology of antimicrobial resistance in institutions and guide efforts to develop more effective strategies for prevention.