According to the Australian Work Health and Safety Strategy 2012-2022, road transport has been identified as a national priority to prevent incidents. Efforts have been made by national regulators to prevent truck-related workplace incidents and accidents. In recent years, much attention has been given to truck drivers’ fatigue management. Increasing evidence suggests that long working hours negatively influence truck drivers’ physiology, health, and safety. However, there is little empirical research in the heavy vehicle transport sector in Australia to identify the influence of working hour management on drivers’ fatigue and consequently, on risk of crashes and injuries. There is no national legislation regulating the number of hours or kilometres travelled by truck drivers. Consequently, it is almost impossible to define a standard number of hours or kilometres for truck drivers in safety management system. This paper reviews the existing studies concerning safe system interventions (e.g. Tachograph), in relation to fatigue caused by long working hours. This paper also reviews the literature to identify the influence of frequency of rest breaks on reducing work-related road/transport accidents involving trucks. Then, a framework is presented to manage truck drivers’ fatigue which may result in reducing the injuries and fatalities involving heavy vehicles.