The use of cannabinoids, commonly referred to as marijuana, for both recreational and therapeutic purposes has been one of the most hotly debated topics in medicine during the past two decades. This chapter reviews the political and economic factors influencing perceptions of cannabinoids and provides a detailed description of the actions of cannabinoids at the level of the microcirculation. The importance of the endocannabinoid system as a major homeostatic system is reviewed. The effects of CB2 receptor activation, providing anti-inflammatory protection without causing a euphoric effect, are described. Potential therapeutic targets, including treatment of stroke, head trauma, traumatic brain injury, spinal cord injury, and multiple sclerosis, are also explored.