A critical review of evidence about the following issues is presented: frequency of depression, clinical picture of depression, suicide, treatment, appearance of disease, terminology, and future trends. In each instance questions that have remained unanswered and may deserve scientific investigation are listed. Although much has been learned already, numerous problems remain unsolved. It is concluded that properly conducted crosscultural research can yield results which can help to resolve the conundrum of depression and respond to the challenge which depression poses to the society, to public health authorities and to the individuals who suffer from it.