In order to manage driver fatigue in transportation it is important to understand the underlying reasons behind fatigue and to recognise that most often fatigue is caused by multiple factors. When designing countermeasures, it is vital that the proposed approach is targeted at the specific problem (cause of fatigue). The most effective approach to fatigue management will include a mix of countermeasures to be deployed in the short, medium, and long term. For any approach to fatigue management to be effective there is a need for shared responsibility. A wide range of involved parties will be influential, including drivers and their families, managers, companies, regulators, unions, and enforcement agencies. This chapter includes a four-step method to evaluate a company’s fatigue situation, understand problem areas, and propose countermeasures that are targeted to be most likely to succeed. This is achieved through the following: (1) understanding the current situation through data collection, (2) synthesising findings into key insights, (3) mapping potential solutions onto identified problems, and (4) implementing countermeasures and review. An open organisational culture is essential for successful fatigue management. A step-by-step approach is likely to be most beneficial, with smaller, easier-to-accept changes being introduced and accepted first before moving up to more sophisticated solutions over time.