Remanufacturing environments involve a higher degree of system complexity when compared to traditional manufacturing environments due to the variability associated with the routing, processing times and demand. Many of the consequences of this system complexity can be dealt with through operational-based approaches using specialized production planning and control techniques. However, it is also possible to improve overall system performance through the analysis of appropriate structural issues such as facility layout. This paper presents the results of a simulation-based analysis of four different layout alternatives: traditional job shop, cellular, fractal and holonic. An analysis of each layout alternative is conducted while varying product complexity, dispatching rules, number of workcenters, number of part types, shop load and demand variability with respect to flow time, WIP and machine utilization. The results of the analysis reveal under which conditions each layout alternative would be preferred to achieve the best overall system performance.