After more than 30 years of research, numerous studies have shown that injection drug use is associated with a wide range of adverse health outcomes such as drug overdoses, drug-related suicidal behaviours, comorbid psychiatric disorders, bloodborne pathogens and other infectious diseases, and traumas. This review explores new trends and prominent issues associated with injection drug use. The dynamic nature of injection drug use is underlined by examining its recent trends and changing patterns in Canada and other “high-income countries.” Three research topics that could further contribute to the development of comprehensive prevention and intervention strategies aimed at people who inject drugs are also discussed: risk behaviours associated with the injection of prescription opioids, binge injection drug use, and mental health problems as determinants of injection risk behaviours.