Drug misuse is associated with serious health consequences and has detrimental effects on military readiness. During 2000 to 2011, 70,104 service members received an incident diagnosis of a substance use disorder (SUD) (excluding alcohol and tobacco-related disorders). Incidence rates declined with increasing age, time in service, rank, and number of combat deployments. Service members in a combat occupation had 1.2 times the rate of individuals in a health care or administation/supply occupation. The median time to discharge after an SUD diagnosis was longest in the Air Force (327 days) and shortest in the Navy (133 days). The substances with the highest incidence rates were cannabis (160 per 100,000 person-years [p-yrs]), "mixed/unspecified/other" (125 per 100,000 p-yrs), and cocaine (61 per 100,000 p-yrs). Incidence rates of cannabis and cocaine use diagnoses generally declined while rates of mixed/unspecified/other and opioid use increased over the surveillance period. The increasing trend in opioid-related diagnoses since 2002 may reflect an increase in prescription drug misuse. The Department of Defense recently expanded its drug testing program to screen for hydrocodone and benzodiazepines.