Cannabis is the most widely used illicit drug in Western counties and its abuse is particularly high in male adolescents and young adults. Its main psychotropic component, the cannabinoid delta-9-tetrahydrocannabinol (Δ9-THC), interferes in the endogenous endocannabinoid system. This signaling system is involved in the control of many biological activities, including the formation of high-quality male gametes. Direct adverse effects of Δ9-THC in male reproduction are well known in both animal models and humans. Nevertheless, the possibility of long-term effects due to epigenetic mechanisms has recently been reported. In this review, we summarize the main advances in the field suggesting the need to pay attention to the possible long-term epigenetic risks for the reproductive health of cannabis users and the health of their offspring.