Objective. Describe the mortality patterns, burden of disease, and mechanisms of injury by homicide in Colombia between 1985 and 2006. Methods. The official population and mortality databases in Colombia were used. Equivalencies of the underlying cause of death were identified and grouped according to the shortlists of the Ninth and Tenth Revision of the nternational Classification of Diseases. The years of potential life lost (YPLL), indices of YPLL, and crude, adjusted, and specific mortality rates associated with major causes and external causes for each sex were calculated. The homicide mechanisms were described. Results. During the study period, a total of 523 870 homicides were recorded (484 475 in men and 39 395 in women). Homicides accounted for 13.8% of total mortality (21.4% of mortality in men and 2.6% in women) and generated 24.2% of YPLL (35.2% in men and 5.8% in women). The highest rates in men were found in the 20–44-year age range, with specific rates of up to 366.9 per 100 000 population, and in women in the 15–40 years age range with specific rates of up to 24.9 per 100 000 population. The most frequent homicide mechanism in both sexes was firearms. Conclusion. Homicides represent a significant burden of disease in Colombia, particularly affecting the young male population. Mortality from homicide has trended downward in recent years.