Inspired by Charles Mackay's 19th-century classic Memoirs of Extraordinary Popular Delusions and the Madness of Crowds, Bernstein engages with mass delusion with the same curiosity and passion, but armed with the latest scientific research that explains the biological, evolutionary, and psychosocial roots of human irrationality. Bernstein tells the stories of dramatic religious and financial mania in Western society over the last 500 years - from the Anabaptist Madness that afflicted the Low Countries in the 1530s to the dangerous End-Times beliefs that animate ISIS and pervade today's polarized America; and from the South Sea Bubble to the Enron scandal and dot-com bubbles of recent years. Through Bernstein's supple prose, the participants are as colorful as their motivation, invariably "the desire to improve one's well-being in this life or the next".

As revealing about human nature as they are historically significant, Bernstein's chronicles reveal the huge cost and alarming implications of mass mania: for example, belief in dispensationalist end-times has over decades profoundly affected US Middle East policy. Bernstein observes that if we can absorb the history and biology of mass delusion, we can recognize it more readily in our own time and avoid its frequently dire impact.