In this chapter, we introduce a new optimization problem that aims at minimizing the reconfiguration cost of a transfer line. A line has to be reconfigured if a new product must be produced by an existing line or any changes in product characteristics occur. In such cases, new operations have to be integrated on existing equipment while some previously assigned operations are deleted. Since transfer lines consist of a sequence of unit head machines, their reconfiguration is not an easy issue because of numerous constraints on compatibility between old and new operations to be taken into account. Therefore, a compromise between introducing new equipment and reusing old one should be found. In this chapter, a Mixed Integer Program is proposed for solving this problem with objective to minimize the cost of the final line configuration. An illustrative example is presented.