Suicide represents a global health concern that encompasses a myriad of biological, psychological, and social factors. Suicide, strictly speaking a manner of death, currently ranks epidemiologically as the 11th leading cause of death in the United States, accounting for approx 30,000 deaths annually. Although reports of suicide have existed since the Greek and Roman times, the trends of suicide specifically in the United States have drastically changed, especially within the past century. The most striking finding is the significant increase in suicide rate for both men and women in the second and third decade of life. The highest suicide rate throughout the 20th century was recorded for Caucasian males and increased with advancing age. In the United States, the national suicide rate decreased by 14% during the last decade of the 20th century, dropping suicide from the 8th to the 11th leading contributory cause of death. Methods of suicide have changed over the century. In 1860, the most common cause of suicide was hanging, which was supplanted by poisoning in 1900. By 1910, and every decade thereafter, death by firearms has prevailed as the primary method of choice. Numerous risk factors have been associated with an increased risk for suicide, such as being divorced or unemployed or suffering from a physical or mental illness. Individuals with a disease of the central nervous system have the highest risk of suicide and may commit suicide within a short time period after diagnosis, or in the late stages of the disease, when the pain and burden have become debilitating. Three mental illnesses most frequently linked to an increased risk of suicide, namely major affective disorder, schizophrenia, and neuropsychological sequelae of chronic alcoholism, are highlighted. The forensic pathologist plays a pivotal role in classifying the manner of death as homicide, suicide, accident, or natural. Both an extensive scene investigation and a thorough postmortem examination with complete toxicological study are warranted in the determination of a suicide. Although “classic” findings at the scene and at autopsy characterize a suicidal death, investigators should be astute to features that may have been intentionally altered to conceal the accurate manner of death. The psychodynamics of the suicide autopsy, which must be realistically evaluated in each case, are discussed in this review. This chapter also addresses causes of suicidal death, including firearm injuries, hanging, stabbing, self-immolation, and overdose. Particular attention to findings at autopsy is addressed. Suicide in the United States is the primary focus of this review because of the wealth of literature and because it is the authors’ country of residence. Nevertheless, an international perspective on suicide with specific consideration of gender differences, adolescent suicide, and self-inflicted death by firearms is presented that correlates well with United States findings. In summary, this review encompasses numerous aspects of suicide, including statistics and trends in the United States, psychosocial characteristics, risk factors, and autopsy findings.