The use of illicit drugs, specifically heroin and cocaine, complicates trauma patient management and consumes extensive hospital resources. This paper focuses on heroin- and cocaine-related injuries observed by physicians at Detroit Receiving Hospital, a large urban Level I trauma center. The pharmaceutical effects, mode of administration, and the manner in which these drugs affect diagnosis and treatment of injuries are documented and discussed. Specific drug-related complications associated with overdose, soft-tissue infections, bacterial endocarditis (therapy resistant), vascular thromboses, vascular aneurysms, vasoconstriction, stroke, cardiac arrhythmias, muscle ischemia, and solid-organ abscesses are also analyzed. Illicit drug use significantly complicates initial diagnosis and trauma management and is associated with severe adverse pathophysiologic effects. Currently, prevention efforts, such as interventions in trauma centers, should be considered as the most efficient and feasible way to prevent injury recidivism in this patient population. We also conclude that legislative change may be the answer in reducing or preventing the horrendous problems caused by illicit drugs.