Medical marijuana remains a highly debated treatment regimen despite removal of state penalties against care providers prescribing the drug and patients treated with the drug in many areas of the USA. The utility of marijuana in specific medical conditions has been studied at length, but its effects on driving performance and risk of motor vehicle collision remain unclear. As with other medications that affect psychomotor function, the healthcare provider should be informed of the potential risks of driver safety prior to prescribing this psychotropic drug to give appropriate anticipatory guidance for appropriate use. The goal of this narrative review is to assess the current literature regarding marijuana as it relates to driving performance and traffic safety. With a foundation in the pharmacology of cannabinoids, we consider the limitations of testing cannabinoid and metabolite concentration. In addition, we will review studies on driving performance and epidemiological studies implicating marijuana in motor vehicle collisions. The increasing prevalence of medical marijuana laws in the USA suggests that clinicians should be aware of marijuana's influence on public safety. Patients should abstain from driving for 8 h if they achieve a subjective "high" from self-treatment with smoked marijuana and should be aware of the cumulative effects of alcohol and other psychoactive xenobiotics.