Introduction: Tobacco use among young people is a complex and serious global dilemma that demands innovative and diverse research approaches. The purpose of this methodological review was to examine the current use of mixed methods research in tobacco control with youth and young adult populations and to develop practical recommendations for tobacco control researchers interested in this methodology. Methods: Using PubMed, we searched five peer-reviewed journals that publish tobacco control empirical literature for the use of mixed methods research to study young populations, age 12±25 years. Our team analyzed the features of each article in terms of tobacco control topic, population, youth engagement strategies, and several essential elements of mixed methods research. Results: We identified 23 mixed methods studies published by authors from five different countries reported between 2004 and 2015. These 23 articles examined various topics that included tobacco use behavior, tobacco marketing and branding, and cessation among youth and young adults. The most common mixed methods approach was variations of the concurrent design in which the qualitative and quantitative strands were administered at the same time and given equal priority. This review documented several innovative applications of mixed methods research as well as challenges in the reporting of the complex research designs. Conclusions: The use of mixed methods research in tobacco control has great potential for advancing the understanding of complex behavioral and sociocultural issues for all groups, especially youth and young adults.