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In this chapter we discuss the Vehicle Routing Problem with Time Windows in terms of its mathematical modeling, its structure and decomposition alternatives. We then present the master problem and the subproblem for the column generation approach, respectively. Next, we illustrate a branch-and-bound framework and address acceleration strategies used to increase the efficiency of branch-and-price methods. Then, we describe generalizations of the problem and report computational results for the classic Solomon test sets. Finally, we present our conclusions and discuss some open problems.