Hospital-associated infection (HAI) in immunocompromised patients can result in high rates of morbidity and mortality. Infections caused by multidrug-resistant organisms (MDROs) are especially worrisome because of the limited choice of remaining antibiotics available when a patient becomes colonized or infected with an MDRO. It is therefore important that immunocompromised patients be cared for in an environment that limits the risk for acquiring infections. However, with healthcare being increasingly delivered in settings other than the traditional inpatient hospital wards, a bigger effort will need to be set forth to prevent or rapidly diagnose HAI. The last few years have seen a significant increase in the number of singleplex and multiplex molecular assays for the detection of many of the organisms responsible for HAI, but more is needed as infections caused by organisms like Legionella pneumophila and Aspergillus species are still diagnosed with methods that have relatively low yield and are slow to provide actionable results. Finally, the use of novel techniques for outbreak investigations will provide new information on transmission of infectious agents in healthcare settings and allow stronger, evidence-based recommendations to be developed for prevention of HAIs in the immunocompromised host.