This chapter provides a public health analysis of imprisonment (the loss of personal freedom for short or long periods—including life sentences): the individual and population effects upon morbidity and mortality including suicide and homicide, drug addiction, and mental health. These effects impact the life course of former prisoners and their families, employment, and life expectancy, and have intergenerational impacts upon the children of incarcerated parents. While international data are presented for comparison of the magnitude and characteristics of imprisonment worldwide, this chapter examines the United States most closely. America is an atypical but instructive case study: the nation with the world’s largest number of prisoners and highest rate of imprisonment. Mass incarceration is not seen in other developed democratic nations but the case of America represents an important natural experiment, demonstrating precisely how high rates of imprisonment can become socially ‘toxic’, with damaging consequences for population health, societal well-being, and human rights.