Suicide continues to be a significant public health issue globally, claiming over 700,000 lives annually. It is, therefore, important to assess the suicide risk properly and provide intervention in a timely fashion. While the heritability of suicidal behavior is around 50%, it does not explain the factors involved in causality. Recent evidence suggests that gene x environment interaction plays a vital role in suicidal behavior. In this paper, we critically evaluate the association between adolescent suicidal behavior and epigenetic modifications, including DNA methylation, histone modification, and non-coding RNAs, as well as epigenetic-based treatment options. It was noted that the prevalence of suicidal behavior in adolescents varied by age and sex and the presence of psychiatric disorders. Childhood adversity was closely associated with suicidal behavior. Studies show that alterations in epigenetic modifications may increase the risk of suicidal behavior independent of mental illnesses. Because epigenetic factors are reversible, environmental enrichment or the use of pharmacological agents that can target specific epigenetic modulation may be able to reduce suicidal behavior in this population.