Cannabis sativa L. is one of the oldest cultivated crops, used for its fiber and medicinal properties. The cannabis plant synthesizes a myriad of secondary metabolites, but the most valuable products from a medical and commercial standpoint are cannabinoids. Despite significant advances in elucidating the biochemistry and genetics that govern cannabinoid accumulation, we still do not have conclusive evidence for the role of these secondary metabolites in the physiology of C. sativa. In line with known functions of other secondary metabolites, the protective functions of cannabinoids against temperature stress, poor micronutrient soil content, drought, ultraviolet B radiation, and as antimicrobial agents have been suggested, but are yet to be conclusively demonstrated. Recent research suggests that the environment has a major effect on cannabis growth and productivity, but the relationship between stress, cannabinoid accumulation, and plant health is complex. Here, we summarize the current insights on how abiotic and biotic stresses affect C. sativa biology. We also examine the available evidence to support the hypothesis for the protective function of cannabinoids against environmental stressors. Maintaining optimal growth and high cannabinoid synthesis is a balancing act, one that can only be achieved by better understanding of the effects of the environment on the cannabis plant.