More than 6 million Americans work night shifts on a regular or rotating basis. The negative consequences of shift work have been established, and recent evidence suggests that patients with shift work sleep disorder (SWSD) are at increased risk of these consequences and co-morbidities. SWSD is a relatively common but under-recognised, and hence undertreated, condition with potentially serious medical, social, economic and quality-of-life consequences. In addition to increased risk of gastrointestinal and cardiovascular disease, patients with SWSD experience clinically significant excessive sleepiness or insomnia associated with work during normal sleep times, which has important safety implications. A number of studies have evaluated countermeasures or interventions in shift workers; proposed treatments include chronobiotic interventions, such as light exposure, melatonin, hypnotic agents, caffeine and CNS stimulants (amphetamine), and the wake-promoting agents modafinil and armodafinil. However, most studies evaluating pharmacological therapies and nonpharmacological interventions simulate night-shift work under conditions that may not accurately reflect real-world activities. Pharmacological and nonpharmacological countermeasures evaluated mostly in simulated laboratory conditions have been shown to improve alertness or sleep in shift workers but have not yet been evaluated in patients with SWSD. To date, three randomised, double-blind clinical studies have evaluated pharmacological therapies in patients with SWSD. These studies showed that modafinil and armodafinil significantly improve the ability to sustain wakefulness during waking activities (e.g. working, driving), overall clinical condition, and sustained attention or memory in patients with SWSD. In conclusion, SWSD is a common condition that remains under-recognised and undertreated. Further research is needed to evaluate different treatment approaches for this condition, to clarify the substantial health and economic consequences of SWSD, and to determine the potential for interventions or treatments to reduce the negative consequences of this condition.