This study assessed the epidemiology of depressive symptoms in Nigerian medical students. A cross-sectional study of 262 medical students from University of Nigeria, Enugu campus, one of the foremost medical schools in Nigeria was studied. Data were collected using structured self-administered questionnaires and the Zung self-rating depression scale developed by Zung as an instrument, which measures the subjective experience of depression. The age range of students was 16-30 years. The prevalence of depression among the students was 23.3%. Students aged 16-20, females, and those who had a professional examination during the period of the study had higher levels of depression, although these findings were not significant. However, students who smoked regularly had significantly higher levels of depression than those who did not smoke. Medical educators in Nigeria need to be aware of the vulnerability of medical students to depression.