Abstract: Quality of life has been defined as a multi-dimensional concept, that includes domains related to physical, mental, emotional, and social dimensions. Along with other prominent factors such as labor market opportunities, education, and housing, health has been identified as a paramount and modifiable factor that can improve the quality of life for not only individuals, but for communities and nations as a whole. Though adolescents in Africa have experienced increases in access to education, more job opportunities, and longer lifespans when compared to previous generations, many inter-connected factors continue to adversely affect their quality of life. Furthermore, given that these adolescents are growing up in a different generation, novel approaches and interventions to impact and improve their health, well-being, and ultimately quality of life are sorely needed. This chapter will explore: (1) general definitions of well-being and its relation to factors associated with quality of life; (2) adolescents in Africa; (3) health burdens in Africa; (4) Serious Games; (5) Games for health on a global scale and (6) Games for health in Africa.