The endocannabinoid system, comprising cannabinoid receptors and their endogenous ligands, has emerged as a key regulatory mechanism in health and disease. The identification of specific cannabinoid receptors (CB1 and CB2) and the development of selective antagonists and inhibitors have facilitated extensive research. The endocannabinoid system is involved in a wide range of physiological functions, including appetite regulation, pain, anxiety, and movement disorders. Modulating this system holds therapeutic promise for various conditions, such as obesity, cancer, and neurological disorders. However, the psychoactive properties of plant-derived or synthetic agonists of CB1 receptors pose a challenge for their clinical use. Selective CB2 receptor agonists, which lack psychoactive effects, represent a promising alternative. The abuse potential of plant-derived cannabinoids can be limited by controlled composition and careful dosing. Preclinical studies and clinical trials with endocannabinoid modulators are likely to lead to novel therapeutic approaches for diseases where current treatments are insufficient. This review provides an overview of the current understanding of the endocannabinoid system as a target for pharmacotherapy.The endocannabinoid system, comprising cannabinoid receptors and their endogenous ligands, has emerged as a key regulatory mechanism in health and disease. The identification of specific cannabinoid receptors (CB1 and CB2) and the development of selective antagonists and inhibitors have facilitated extensive research. The endocannabinoid system is involved in a wide range of physiological functions, including appetite regulation, pain, anxiety, and movement disorders. Modulating this system holds therapeutic promise for various conditions, such as obesity, cancer, and neurological disorders. However, the psychoactive properties of plant-derived or synthetic agonists of CB1 receptors pose a challenge for their clinical use. Selective CB2 receptor agonists, which lack psychoactive effects, represent a promising alternative. The abuse potential of plant-derived cannabinoids can be limited by controlled composition and careful dosing. Preclinical studies and clinical trials with endocannabinoid modulators are likely to lead to novel therapeutic approaches for diseases where current treatments are insufficient. This review provides an overview of the current understanding of the endocannabinoid system as a target for pharmacotherapy.