When Europeans discovered tobacco among Amerindians in the New World, it became a long-sought panacea of panaceas, the critical ingredient in enemas, ointments, syrups, and powders employed to treat everything from syphilis to cancer. Almost five centuries passed before medical researchers concluded that tobacco is unhealthy and can cause cancer.

Smoke Signals follows tobacco from its origins in South America's Andes through its checkered history as a "miracle cure," powerful addictive and poison, friend of government revenue departments, and enemy of law enforcement directed at contraband and tax diversion. Author Jim Poling, Sr., traces tobacco's sacredness among Natives, notably how the modern substance has changed Native lives, sometimes for the good, often for the bad, explores how the coffers of governments, now so dependent on tobacco revenue, will be affected if the plant's commercial use is eliminated, and examines how Native traditions, including tobacco as a holy herb, might survive in modern society and strengthen Natives.