Drug overdose is a major cause of death among homeless people, but little is known about the characteristics of homeless overdose decedents. We conducted a retrospective record review of 219 adult patients of Boston Health Care for the Homeless Program (BHCHP) who died of drug overdose in 2003-2008. We assessed the substances implicated in overdose and the health and service use characteristics of decedents prior to death. Eighty-one percent of overdose deaths involved opioids and 40% involved multiple drugs. Problem substance use (85%), psychiatric illness (61%), and chronic pain (45%) were common, and 32% had documentation of all three. Half were well-connected to BHCHP, and 35% had a clinic visit within 90 days of death. The complex health histories and frequent health care contacts of homeless drug overdose decedents suggest that clinical facilities may be an important frontline venue for overdose education, naloxone distribution, and integrated substance use treatment programming.