Manufacturing companies face rising pressure due to increased competition. Traditionally, companies have merely concentrated on offering impeccable, cost-efficient products. Today, however, flexibility and on-time delivery are additional requirements to satisfy the customers. At the same time, disruptions in production, especially in low-volume assembly, still frequently occur, leading to economic losses and delayed customer deliveries. The approach proposed in this paper strives for improving the disruption situation in low-volume assemblies. A detailed disruption management methodology has been developed, aiming at realizing an efficient reduction of disruptions, while at the same time considering the specific characteristics of low-volume assembly. The methodology is supported by a catalog of pre-emptive measures. These measures are known to reduce the disruptions’ occurrence or to diminish their consequences. In general, the approach pursues the basic idea to implement particularly those measures, which have the best cost-benefit-ratio. Based on the analysis of the cost-benefit-ratio of each measure, the developed methodology aims at improving the disruption situation in assembly and thus providing a high on-time delivery rate. The usability of the methodology for the low-volume assembly context has been confirmed by assembly experts on the basis of an application of the methodology in an exemplary case study.