Introduction: Substance use has been a menace throughout the world for several centuries, and adolescents seem to be the most vulnerable group and the miasma of the slums adds to this multi-dimensional problem. Objectives: To study the prevalence and pattern of substance use among adolescents living in slum of Guwahati. Materials and Methods: A cross-sectional study was conducted among the adolescents living in slums of Guwahati, Assam, India during February to May 2014. Out of the total 90 slums, 23 slums were selected by cluster sampling method. For the selection of desired clusters probability proportionate to size method was applied. From each slum, equal number of boys and girls were interviewed to get a total of 414 study subjects. Statistical Analysis: Proportions and mean were used. Results: Prevalence of ever users was 37.68% and 35.02% were current users. Prevalence of substance abuse and dependence were 8.33% and 5.13% respectively. Gutkha (83.4%) was the most common substance used. The proportion of the substance users was found to increase significantly with age in both the sexes. The mean age of initiation of the abusive substances was 12.08 (±2.009) years for males and 12.38 (±1.803) years for females. The most common reason for initiation was peer pressure (73.1%). Shops were the main source of procuring substances. Conclusion: As significant number of adolescents is resorting to substance use, especially under the influence of peers, intensive peer group counseling is advocated. Strict implementation of legislations is emphasized, so that these young generation have no access to these dangerous substances.