With some 70 characters and a wide array of events spanning 500 years and several continents, the plot of this novel is less a linear plot than an elaborate web of events. Peopled with addicts, alcoholics, corrupt judges and politicians, unscrupulous and greedy land speculators, and a host of other unsavory characters, the novel also tells the story of resistance to Euro-American oppression and a growing effort of indigenous people and their allies to retake the land and ultimately to become agents of its healing. Woven throughout the novel are folk stories of the past, pronouncements on the present and predictions of a dire future for the offspring of the European conquerors.

Spatially, Tucson, Arizona functions as a focal point, with much of the action radiating away from, or towards, the city. Arizona is about to go belly-up from the effects of a declining economy and devastating drought and growing civil unrest in Mexico. As the prophecies have foretold, the narrator reminds readers, the inexorable movement of the people is North, and while it may take 500 or 5000 years, the indigenous and their allies will reclaim the diseased and corrupted land (and presumably become instruments of its healing).

Into this milieu Silko inserts a host of characters who work as part of the resistance. Among them are twin sisters Lecha (a demerol-addicted psychic who helps police locate the bodies of murder victims and has a lucrative profession as a talk show guest) and Zeta (who has made a fortune running drugs and guns across the North and South American borders with the help of Lecha’s son and his sometime lover Paulie); twin brothers, Tacho (a chauffeur for the wealthy Menardo who also functions as a spy for the indigenous resistance movement), and El Feo (who heads that movement in the far South of Mexico). Both brothers commune with spirit macaws for advice.

There is an "army of the Homeless" who plan to retake "stolen" goods and land from the wealthy. The Barefoot Hopi organizes incarcerated prisoners for an uprising against the U.S. Government. Many of these and other characters converge at novel’s end at the International Holistic Healer’s Convention where "German root doctors" and "Celtic leech handlers" join with "new-age spiritualists" and the Green Vengeance eco-warriors.