While molecular typing methods are widely used to help the epidemiologist in the investigation of outbreaks, their use for the investigation of endemic infections has been limited. For the investigation of a micro-epidemiological setting such as the understanding of endemic nosocomial infections, discriminant methods are needed, such as pulsed field gel electrophoresis (PFGE), or PCR related typing methods. However, for long-term surveillance, preference should be given to typing methods that give definite results. The identification of the source or reservoir is only possible with comprehensive screening of the environment and the endogenous flora of patients and staff, and therefore, requires significant resources. However, cross-contamination or the existence of a common exogenous source might be investigated by typing clinical isolates during non-epidemic periods. Cross-contamination is suspected when isolates from different patients belong to the same type and when an epidemiological relation can be established. Thus, molecular typing makes it possible to track the dissemination of specific clones, it may facilitate the breaking down of endemic transmission to the level of micro-epidemics. This is illustrated by the example of one investigation of Pseudomonas aeruginosa colonization/infection in patients hospitalized in intensive care units.