Respiratory epithelium cancers are the leading cause of cancer-related death worldwide. The multistep natural history of carcinogenesis can be considered as a gradual accumulation of genetic and epigenetic aberrations, resulting in the deregulation of cellular homeostasis. Growing evidence suggests that cross-talk between membrane and nuclear receptor signaling pathways along with the activator protein-1 (AP-1) cascade and its cofactor network represent a pivotal molecular circuitry participating directly or indirectly in respiratory epithelium carcinogenesis. The crucial role of AP-1 transcription factor renders it an appealing target of future nuclear-directed anticancer therapeutic and chemoprevention approaches. In the present review, we will summarize the current knowledge regarding the implication of AP-1 proteins in respiratory epithelium carcinogenesis, highlight the ongoing research, and consider the future perspectives of their potential therapeutic interest.